These letters concern various scientific subjects, such as fishes, insects, snakes, mice, fossils, and mosses. Other subjects include learned institutions, notably the Smithsonian Institution and the Academy of Natural Sciences of Philadelphia, and men of science. Correspondents include S. S. Haldeman, Walter J. Hoffman, Spencer F. Baird, Edward D. Cope, and Leo Lesquereux.

The primary correspondence (ca. 65 letters) is with William Cooper (1798-1864) on Bonaparte's publications, especially "American Ornithology" and "Observations on the Nomenclature of Wilson's Ornithology," but also included are many references to American and European men of science and learned societies. There are also letters to Isidore Geoffroy Saint-Hilaire, George Robert Gray, Titian Ramsay Peale, and Wilhelm P. S. Rüppell.