On March 23, 1806, the Corps of Discovery left Fort Clatsop, their winter quarters on the Pacific Coast, and started back up the Columbia River on their long return journey to the United States. It was now nearly two years since they had left St. Louis bound west; if they could get across the Rocky Mountains by the Lolo Trail early enough, they could descend the Missouri River before it froze and reach their starting point in this same year. They were now largely retracing a route they had already followed and so did not bother with the detailed courses and distances of the outbound journey, but their journals were still filled with the incidents of the voyage and descriptions of the country and its people.

There was still room for new discoveries; on the way down the Columbia they had missed the mouth of the Willamette River, concealed behind islands. They encamped for a week on the north side of the Columbia to hunt and take astronomical observations, while Clark made a quick exploration a few miles up the new stream. The captains called it the Multnomah after the Indian name and regarded it as coming from much deeper in the continent than was really the case. On April 6 the party was again on its way.

They were nearly two weeks getting upriver past the Cascades and the Celilo Falls. To the wearisome labor of portaging was added the aggravation of bad relations with many of the Indians in the vicinity. The natives demanded high prices for any food they sold, and some of them could not resist stealing. The captains' patience was at low ebb and they threatened violence if stolen goods were not returned. When some Indians made off with Lewis's dog Seaman, Lewis sent a party of men to recover his friend and companion, with orders to shoot if necessary. Fortunately, no one was killed and Seaman was returned to the Corps.

Once past the falls they traded canoes for horses to continue their journey by land and made their way up the north side of the Columbia to the Walula (or Walla Walla) Indians, whom they found much more hospitable than those lower down the Columbia. On the westward journey the captains had promised Chief Yelleppit that they would remain with him for a few days on the way back. They kept their promise and camped with the Walulas from April 27 to 29, at the mouth of the Walla Walla River. Yelleppit told them about an overland shortcut to the Nez Perces, so on the thirtieth they continued eastward by land following a Nez Perce guide they had met several days earlier. They were anxious to reach the Nez Perces, with whom they had left their horses on the westbound trip.

This eastbound trip took the party over new ground; going west they had traveled by canoe down the Clearwater and Snake rivers to the Columbia. With the advice of their guide they now took the shortcut between the Walla Walla and the Snake, passing the present towns of Waitsburg, Dayton, and Pomeroy, Washington. They reached the Snake a little below the mouth of the Clearwater. On the way they met Wearkoomt, a Nez Perce chief who had been helpful to them on their way down the Snake the previous fall. Having reached the Snake and crossed it on May 4, the party continued up its north side to the Clearwater and up the north bank of that river.

Here in the Nez Perce country, in modern west-central Idaho, the captains assumed a new and demanding role as physicians to the local people. On the westward trip some medicines they had prescribed had eased the ailments of several patients, and had, said Clark, "given those nativs and exolted oppinion of my skill as a phisician." During a period of nearly six weeks that they were forced to remain with the Nez Perces in May and June of 1806 they were visited by a host of the afflicted, suffering from a variety of ills, notably rheumatic complaints, sore eyes, and abscesses. Lewis was doubtful if any permanent cures could result, but the immediate benefit to relations with the Nez Perces was so great that he decided to continue treatment, wishing that they could indeed cure these "poor wretches."

The captains also had to mediate a dispute between the local Nez Perce leaders. The previous fall they had left their horses with the hospital chief Twisted Hair; some more prominent chiefs who had then been absent were vexed with him on returning, thinking that he had presumed too much in taking on the responsibility. Twisted Hair, disgusted with their criticism, had let the horses wander over a considerable area. Now Lewis and Clark did their best to reconcile the squabbling chiefs so that their animals could be recovered.

On May 14 the party settled in to a camp on the east side of the Clearwater at the modern town of Kamiah, Idaho, where they would remain for nearly a month. The Nez Perces told them that it would be at least that long before the snows in the Bitterroot Mountains melted sufficiently to allow passage east over the Lolo Trail. Their campsite has come to be called Camp Chopunnish after the explorers' name for the Nez Perces. The party passed their time seeking food, counciling and socializing with the Nez Perces, and obtaining more horses for the next stage of the trip.

Some further medical problems engaged their attention during this lengthy sojourn. William Bratton had been suffering ever since Fort Clatsop from a mysterious back ailment which had virtually incapacitated him. No other remedy having worked, the captains tried a sweat bath suggested by John Shields, the extreme heat being alternated with immersion in a cold mountain stream. In a short time Bratton's back loosened up and he was able to walk again. Another patient was a Nez Perce chief who had suffered from paralysis for five years, with no apparent cause. For lack of a better remedy the captains subjected him to the sweat-bath treatment, and to their amazement he began recovering the use of his limbs.

Naturally, the two leaders continued their studies of natural history, native culture, and geography. Clark gathered what information he could about country to the north and south of the party's trail, together with the locations of Indian tribes, obtaining maps from the Nez Perces. Lewis continued his study of the grizzly bears, concluding that in spite of their many color variations they were all of the same species. He also discovered the cinnamon bear, a western color variant of the familiar black bear. A number of new animals and plants were described, including the pigmy horned lizard, western tanager, Columbian ground squirrel, beargrass, and ragged robin. It was probably here that they collected what seems to be the only zoological specimen of the expedition to have survived to the present day, the skin of a Lewis's woodpecker. In the land of the Nez Perce Lewis also made another discovery of a root much like the sweet potato. Lewis's description of cous (his "cows") is unmistakable; it constituted one of the basic food sources for natives in the region.

In council Lewis and Clark promised the Nez Perces that American traders would soon follow them to provide the Nez Perces with trade goods, especially guns with which to defend themselves against the Blackfeet and other enemies. They also promised, if they should meet the Blackfeet on their eastward trip, to try to persuade them to make peace with the Nez Perces. Their hosts may have been a bit skeptical on this point, but the hope of obtaining weapons to match those of their enemies inspired even greater regard for their visitors. The men found much to admire about their hosts' customs, hospitality, and appearance. The traveling ethnographers recorded much about Nez Perce material culture during the forced stay. Food, clothes, and housing, of course caught their attention and the horse culture of this equestrian people was also a matter of serious consideration. Finally, the captains tried to explain Nez Perce attitudes, ceremonies, and rituals in their journals.

By June 9, 1806, the captains decided to begin their move eastward. According to the Nez Perces the snow would not be gone from the mountains along the Lolo Trail until the beginning of July, but the whole party was anxious to start homeward, so they left the valley of the Clearwater for the flats above the river, "exolted," Clark says, "with the idea of once more proceeding on towards their friends and Country."