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.

A leading national opinion maker and influential regional politician, tied by marriage to the families of Benjamin Franklin and cognate families, William Duane (1760-1835) played key roles in the field of political journalism, as well as national, Pennsylvania and local Philadelphia politics. Editor of the Aurora, William Duane (1760-1835) assured himself gratitude from Jefferson and the Republicans and enmity from President Adams and the Federalists for his open and effective attacks on Federalist policies. His son William John Duane (1780-1865), was a prominent member of the Pennsylvania legislature, a legal advisor to Stephen Girard, Solicitor for many of Philadelphia's premier institutions, and Secretary of the Treasury of the United States (June-September 1833). The Duane Family Collection contains a diverse assemblage of personal and professional correspondence relating to family members, with interesting material relating to William Duane (1760-1835), his son, William John Duane (1780-1865), grandson William Duane (1808-1882), great-grandson Charles Williams Duane (1837-1915), and other relations. The collection includes unique correspondence from and relating to Benjamin Franklin's family, as well as correspondence with Thomas Jefferson and other leading figures from the early nineteenth century. The collection also includes prints, photographs of family members, as well as some maps.