David Rittenhouse (1732-1796) was one of the most prominent American men of science of the 18th Century. A skilled instrument maker, Rittenhouse was the an astronomer, playing a major role in recording the 1769 Transit of Venus, among many accomplishments. Rittenhouse also conducted important survey work for the state of Pennsylvania, establishing the state's western border, as well as overseeing the completion of the Mason-Dixon survey. In addition to his scientific endeavors, Rittenhouse's work for American independence places him among the important founding fathers. Subordinating his scientific interests for the greater good of Pennsylvania during the American Revolution, Rittenhouse served as a member of both the Pennsylvania Assembly and the Pennsylvania Constitutional Convention, and held powerful positions on the Pennsylvania Council of Safety and the subsequent Committee on Safety. Rittenhouse also served as the first director of the United States' Mint, at the behest of President George Washington. Rittenhouse was elected to the American Philosophical Society in 1768 and played a major role in placing the Society on the scientific map. He held many positions in the Society, including serving as its President from 1791 until his death in 1796. The Rittenhouse papers span 1774 to 1932, and consist of 61 items, over 0.25 linear feet. The collection is comprised mainly of correspondence, but also includes receipts, genealogies and broadsides.

An important 18th century radical republican theorist and political writer, Thomas Paine was a leading figure in the American Revolution. Despite his humble beginnings and lack of formal education, his reasoned and persuasive writings not only influenced nascent American republican ideology, but profoundly affected the perception of government in England and France as well. His three most influential works are Common Sense (1776), The Rights of Man (1791-1792), and The Age of Reason (1794, 1795, 1807). The Richard Gimbel Collection is a heterogeneous mix of items connected only by the fact that they were all collected by Gimbel (1898-1970) and that most were written by, to, or about the revolutionary Paine. Of primary importance are the approximately sixty-five letters or manuscripts in Paine's own hand, including Paine's 1776 manuscript notes for Common Sense, his letter of January 10, 1781, in which he takes leave of his former commanding officer, Nathanael Greene, and his January 6, 1789 letter to Kitty Nicholson Few, in which he writes of his view of matrimony and other personal matters. The collection includes a series of correspondence between Thomas Paine and Samuel Adams, which were originally marked "forgeries," these appear instead simply to be the letters of two men bearing famous names.

The Thomas Jefferson papers contain a large number of correspondence both to and from Jefferson, as well as various other material related to American Revolutionary War and Early Republic. Includes correspondence with Patrick Henry, Charles Willson Peale, Richard Henry Lee, Horatio Gates, David Rittenhouse, Robert Patterson

A physician, natural historian, and professor at the University of Pennsylvania, Benjamin Smith Barton (1766-1815) was one of the central figures in Philadelphia's early national scientific establishment. Having received his medical training in European universities, Barton was appointed Professor at the University of Pennsylvania in 1789, lecturing on botany, materia medica, natural history. A prolific author, he established his reputation as one of the nation's preeminent botanists through his botanical text book The Elements of Botany (1803), but his contribtions to zoology, ethnology, and medicine were equally noteworthy. Barton's monograph on the "fascinating faculty" of the rattlesnake and his efforts in historical linguistics (New Views of the Origin of the Tribes and Nations of America, 1798) were widely read, and his Philadelphia Medical and Physical Journal (1804-1809) was one of the nation's first medical journals and an important outlet for natural historical research. The Barton Papers offer a comprehensive view of the professional work of Benjamin Smith Barton from the time of his return to the United States in 1789 until his death. The collection is divided into five series: Correspondence, Subject Files, Bound Volumes, Graphic Materials, and Printing Plates. The collection includes a particularly valuable series of botanical, medical, and natural historical drawings collected by Barton for research, reference, and publication. Among the many artists represented are William Bartram, Frederick Pursh, Pierre Turpin, and Benjamin Henry Latrobe.

Though the Miscellaneous Manuscripts collection is composed of items that do not fall readily into any other existing collection, the two dominant intellectual areas represented in the collection are Early American History and History of Science.