Series 4 contains Mitchell's correspondence with physicians, literary figures, and other acquaintances. The letters are original, unless otherwise noted on the finding aid, and in some cases, a run of correspondence is accompanied by a letter explaining its provenance. Subseries 4.1 consists of a disbound letterbook containing resolutions from various societies and sympathy letters on the 1858 death of Mitchell's father, John Kearsley Mitchell; included are letters from Robley Dunglison and Samuel Henry Dickson. S. Weir Mitchell's correspondence with American and British physicians is contained in Subseries 4.2; included are letters from John Shaw Billings, Sir Lauder Brunton, Harvey Cushing, Simon Flexner, Fielding H. Garrison, George M. Gould, J. Hughlings Jackson, William W. Keen, Hugo Munsterberg, Hideyo Noguchi, Sir William Osler, Sir James Paget, W. S. Playfair, Sir D'Arcy Power, Sir Ronald Ross, Beverley R. Tucker, Sir John Batty Tuke, and J. William White.
Correspondence with literary figures is in Subseries 4.3. Included are letters from Richard Watson Gilder, Oliver Wendell Holmes, Henry Charles Lea, George Meredith, Elizabeth Stuart Phelps, Howard Pyle, Agnes Repplier, James Ford Rhodes, James Whitcomb Riley, A. L. Wister, and Owen Wister. Also included is Mitchell's extensive correspondence with Amelia Gere Mason (170 items) and Sarah Butler Wister (106 items). Both women, who were among Mitchell's closest friends, offered support and advice on personal and literary matters. General correspondence with friends and acquaintances is in Subseries 4.4; correspondents include Andrew Carnegie, Danske Dandridge, professor Max Farrand, artist Frank Holl, Frances Butler Leigh, Louisa S. Minot, Anne Thackeray Ritchie, Agnes M. Swann, William H. Taft, Charles D. Walcott, and Owen Jones Wister. Correspondence and papers relating to studies of patients with nerve injuries are also in Series 4. Included is the correspondence of S. Weir Mitchell and John K. Mitchell, both of whom conducted follow-up studies of the patients S. Weir Mitchell treated during the Civil War; these studies were included in John K. Mitchell's Remote Consequences of Injuries of the Nerves and Their Treatment (1895). In addition to correspondence, Subseries 4.5 contains completed patient questionnaires, case reports, and miscellaneous papers. Finally, Series 4 contains miscellaneous correspondence pertaining to nursing, fear of cats, psychotherapy, and a proposed monument to Civil War surgeons. Also present are letters from John Bigelow, Horace Howard Furness, William Dean Howells, and James Whitcomb Riley, in which the correspondents respond to Mitchell's queries about their sleep and dream experiences; the finding aid contains an item-level calendar of these items.