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The General Manuscript Collection is an artificial collection of correspondence, diaries, lecture notes, class work, essays, administrative documents, minutes, and other documents collected by the Rare Book & Manuscript Library. Single items or very small collections are generally classified as part of the general manuscript collection rather than assigned an individual manuscript number. Additionally, small additions to existing RBML manuscript collections may be classified as part of the General Manuscript Collection.

Papers of the Jay family and of those families related to the Jay family, including Bruen, Butterworth, Chapman, Clarkson, Dawson, Du Bois, Field, Iselin, McVickar, Mortimer, O'Kill, Pellew, Pierrepont, Prime, Robinson, Schieffelin, Von Schweinitz, Sedgwick, and Wurts. In addition to family and personal matters, the correspondence deals with anti-slavery, New York State civil service, repeal of the Missouri Compromise, the Civil War, the Blair Bill, international affairs, and New York City and State politics and government. There are letters from numerous prominent persons including George Bancroft, F.A.P. Barnard, Bismarck, William Cullen Bryant, Aaron Burr, James Fenimore Cooper, Ralph Waldo Emerson, Hamilton Fish, Albert Gallatin, Horace Greeley, Nathaniel Hawthorne, Oliver Wendell Holmes, Washington Irving, Frances Anne Kemble, Jenny Lind, Henry W. Longfellow, Seth Low, James Russell Lowell, John Stuart Mill, Alice Duer Miller, Clement Clarke Moore, J.P. Morgan, Thomas Nast, Commodore Matthew Perry, Franklin D. Roosevelt, Theodore Roosevelt, Elihu Root, Carl Schurz, William H. Seward, William T. Sherman, Charles Sumner, and John Greenleaf Whittier.