During the eighteenth century, Cayuse Indians lived along the headwaters of the Walla Walla, Umatilla, and Grande Ronde Rivers, in present-day Oregon and Washington. Today, most Cayuses live in Umatilla County, Oregon, and in regional cities and towns.
Largely because of their enormous herds of horses, the Cayuses became so wealthy during this period that they no longer bothered to fish, trading instead for fish and other necessities. They welcomed the Meriwether Lewis and William Clark expedition in 1806 and welcomed as well the fur traders who entered their territory shortly after the explorers' coming. They were not especially interested in furs but rather in the manufactured goods of non-Indians that they might trade for. Their openness to non-Natives was also due in part to their luck at having so far escaped most of the disease epidemics that ravaged other Indian peoples.
The first Presbyterian missions in the area opened in 1836. In 1843, the first emigrants traveled on the Oregon Trail. In 1847, relations between the Cayuses and whites, hitherto friendly, took a dramatic turn for the worse when a group of Indians destroyed the local mission and killed its founders, Marcus and Narcissa Whitman, and others. They blamed the missionaries for the disease epidemics that were destroying their people. They also resented the Whitmans for their intolerance to the Indians and their new wealth based on sales of former Indian land.
The Whitman "massacre" was the opening salvo in a constant struggle with non-Natives (the Cayuse War) that lasted until about 1850. Tiloukaikt, a band chief and former friend of non-Native traders, was a leader in this conflict. The tribe was ultimately defeated, and some of its members were hanged by the U.S. government. By this time, disease, warfare, and intermarriage with the Nez Percé had greatly reduced the tribe. Although the Cayuses kept up sporadic resistance into the 1850s, they were assigned by treaty to the Umatilla Reservation in 1855, and most were removed there in 1860. Some Cayuses took up farming on the reservation. Some joined the Yakimas (1855), Nez Percé (1877), and Bannocks (1878) in their various wars against the whites, but some also served with the U.S. Army during these wars.