The bulk of this series comprises letters that Narcissa Whitman and Marcus Whitman sent to Narcissa Whitman's family and friends. Recipients include Narcissa Whitman's parents, Stephen Prentiss and Clarissa Prentiss; Narcissa Whitman's siblings and in-laws Clarissa Kinny, Edward Prentiss, Harriet P. Jackson, Jane Prentiss, Jonas Galusha Prentiss, and Lyman Judson; and missionary wives Elvira Perkins and Laura Brewer. These letters describe the overland journey that the Whitmans made in 1836, their lives and activities as missionaries, and their opinions on matters such as Euro-American emigration to the Oregon Territory and the Whitmans' concerns about the presence of Catholic missionaries in the region. A number of Narcissa Whitman's letters were written over a period of time, in some cases over the course of several months, before being sent. Many of these letters contain patronizing or derogatory sentiments regarding Native peoples, caused both by the Whitmans' disapproval of Cayuse cultural norms, and by their frustration with the Cayuse's reluctance to convert to Calvinist Christianity. Unless otherwise noted, all of these letters are originals that Oregon Historical Society founder George Himes obtained in the early 1890s from Narcissa Whitman's sister, Harriet P. Jackson.

The rest of the series contains typescripts of the Whitmans' correspondence with the American Board of Commissioners for Foreign missions, other missionaries, and U.S. government officials. With the exception of an 1836 letter from David Greene to Marcus Whitman copied by Clifford M. Drury, and a copy of a letter and proposed legislation from Marcus Whitman to the U.S. War Department, these typescripts were most likely made by Oregon Historical Society staff based on originals at Harvard University's Houghton Library and elsewhere.