The collection of about 850 items covers the period from 1782 to c. 1936, with the bulk dating to the 1780s to 1840s. The collection is divided into four series. Series I contains correspondence relating to a wide variety of topics, including French and English politics, business, trade, religious matters, and personal affairs. Many of the items are letters of introduction. There is also information on John Vaughan's immigration to America, Joseph Priestley, vaccines and inoculation (with Jefferson's comments on the same), Vaughan's business in Philadelphia, and the American Philosophical Society. Also included in this series are 2 boxes with copies of Vaughan correspondence as well as miscellaneous notes by E. W. Madeira, gathered in the course of his research on Vaughan in the 1930s. Series II consists of three volumes. Included are two of Vaughan's commonplace books. One, entitled, "J. Vaughan's book," May 17, 1779 (47 pp., in Latin; 870/L34), includes mostly Latin notations. The other commonplace book, dated 1783 (ca. 66 pp.; B V 462.c), includes comments on several prominent Americans, such as Benjamin Rush and David Rittenhouse, as well as American society generally. The third volume is a copybook with thirty letters spanning the period 1784 to 1801 (B V462.1). Series III includes material relating to Vaughan's administration of the estate of the Philadelphia merchant Samuel Merrick, 1796-1822 (Vaughan-Merrick Papers, B V462.m; 2 boxes). Series IV consists of correspondence between Vaughan and the DuPont Co. for which he served as agent (B V462.4; photocopies of 73 letters).

This collection includes letters from, and drafts of letters to, scientists, artists, musicians, soldiers, political figures, and court personages throughout Europe, especially Italy and France. Topics covered range from personal and social affairs to agriculture, botany, geology, natural history, coinage, museum management, politics, weights and measures, current affairs. The collection also includes four diaries, housed separately with manuscript volumes.

The Calendar of the Papers of Benjamin Franklin prepared by Isaac Minis Hays for the bicentennial of Franklin's birth in 1906 provides access to the largest portion of the Franklin Papers at the APS. The items were originally bound into volumes in roughly chronological order, with letters to Franklin preceding those from Franklin and at the end of the collection, Franklin's letters owned by the University of Pennsylvania. Each manuscript is still identified by Hays' reference numbers, which include a roman numeral refering to the original volume followed by an arabic number to identify the folio. The electronic version of the finding aid replicates Hays' calendar, including the introductory material and item-level descriptions. It has been updated to reflect corrections in the metadata, corrections of personal names, dates, and description.

Through his craniometic studies of human races, the Philadelphia physician Samuel George Morton (1799-1851) exerted a profound influence on the development of physical anthropology in antebellum America, and made substantial contributions to mineralogy, paleontology, and natural history. Relating primarily to Morton's scientific interests, the Morton Papers include insights into Morton's perspectives on education, medical practice, geology and mineralogy, craniology, paleontology, the Wilkes Exploring Expedition (also known as the United States Exploring Expedition 1838-1842), and his two major monographs, the Crania Americana and Crania Aegyptiaca. Several of the letters were written by Morton in his capacity as corresponding secretary of the Academy of Natural Sciences of Philadelphia. Also included in this collection are Morton's "Some Remarks on the Infrequency of Mixed Offspring Between the European and Australian Races" (1850), Joseph Barclay Pentland's notes on the aborigines of Peru (ca. 1840?), and newspaper clippings on Morton's death; a diary of Morton's trip to the West Indies, 1834, a set of craniological sketches for use in Crania Americana, and a microfilm of letters in private hands, written to Morton, 1838-1844