By 1836 both the Presbyterians and the Jesuits had penetrated the Pacific Northwest. The Whitmans and the Spaldings were the first Presbyterians to settle in this region. The Whitmans settled with the Cayuse at W ailaptu near Walla Walla and the Spaldings resided at Lapwaii with the Nez Perce tribe. Although two Canadian priests were working in this region, it was not until 1840, with the arrival of Father Jean-Pierre DeSmet that the Jesuits commenced their missionary work. Fr. DeSmet initially settled with the Flathead tribe in the Bitterroot Valley of Montana. This paper observes how the Jesuits in Montana and the Presbyterians in the Columbia basin related with their respective tribes. With each situation a pattern occurs of tribal acceptance and rejection. The different tribes were initially eager to learn from the missionaries but as the years pass by, the novelty of Christianity wore thin. What became more obvious to the tribal members was that slowly their numbers were diminishing due to disease brought over by white settlers and simultaneously their land was disappearing as the pioneers built their homes. This observation resulted directly in the Native American rejection of the Christian missionaries. The Jesuits and the Spaldings were fortunate to escape without physical harm. This was not the case, though for Dr. Marcus and Narcissa Whitman who lost their lives in the Whitman massacre. To understand the reasons for this rejection, this paper spends the first few chapters looking into the background of the three tribes as well as the missionaries. It then examines the three different tribes and their history with their respective missionaries, observing the reasons, both long and short term for their failures. In the final chapter the paper investigates the obvious yet undocumented competition between the Catholic and Protestant missionaries to be the sole religion in this region. Their co-existence of these two faiths was another factor which resulted in the disillusionment of the Native American tribes in this region.