This collection contains material relating to his legal affairs, medical publications, receipts for books purchased, and information on botany. Important correspondents include Edward H. Clarke, George Mifflin Dallas, Samuel David Gross, and Joseph Henry. There is also family history in these papers.

The correspondence is principally to Zaccheus Collins (1810-1840), with bills, receipts, and notes on Rafinesque vs. Parker; letters from Collins, L.A. Tarascon, Lewis C. Beck, John Torrey, and Charles W. Short (1817-1835); and miscellaneous correspondence and documents relating to Rafinesque vs. Parker, with an account of the Felician Society of Feliciana County, Illinois (1820). The writings are chiefly on botanical topics, and include notes and essays on Indians, Blacks, grapes and wine-making, banking, and speculation. Rafinesque's growing interest in Indian antiquities, linguistics, and history is apparent in letters after 1820. There is an account of Rafinesque's scientific travels in North America and southern Europe (1800-1832), and a bibliography. The botanical notes include descriptions of specimens collected by Lewis and Clark, Patrick Gass, and Henry Muhlenberg.