The first several letters of this collection are largely those of the John Hemphill (1761-1832). There are several boxes of Associate Reformed Presbyterian sermons, and many of the earlier letters relate to affairs of that church in South Carolina, including many letters from other ministers of that faith to William Ramsey Hemphill. Three sermons and a pastoral letter of William Ramsey, as well as letters from N.M. Gordon, William W. Patton, Matthew Linn, Samuel Taggart, James Hemphill, and Robert C. Grier to him, concern the question of slavery. These letters are by other A.R.P. ministers and relatives.

Along with religious correspondence, there are letters discussing: naturalization laws in force in 1807; Aaron Burr's expedition; anti-Masonic meetings in Alabama in 1820; nullification sentiment in South Carolina in 1832 and anti-nullification sentiment in North Carolina as expressed in a letter from 1833; pro-slavery views; resignation of Thomas Cooper as president of South Carolina College; movement of slaves through Augusta, Georgia, in 1834-1835; expedition of 1836 against the Seminoles of Florida; affairs at South Carolina College; abolition petitions in Congress in 1836; attempts to link Charleston with Cincinnati by rail; presidential campaign of 1840; Catholic support of Temperance in Philadelphia in 1840, and other aspects of the Temperance movement; movement of John Hemphill to Texas in 1838 and his elevation to the supreme court of that state in 1840; African Colonization Society; John Hemphill's service with an expedition against the Mexicans in 1843; encounter with Sam Houston and his wife in 1845; sending of missionaries to Liberia; establishment of a mail steamship line from Charleston to Havana; Calhoun and Clay in 1849; Erskine College and Erskine Theological Seminary; Stockton, California, and vicinity in 1851, as described by Robert King Reid (he and John Y. Lind had gone to California from South Carolina. He was elected resident physician at the California state hospital, and Lind was elected to the California senate); American Colonization Society; presidential election of 1856; slavery controversy in Kansas and land prices there; abolition; secession; reception in the South of the speeches of Stephen Douglas and reception in the North of William L. Yancey's speeches; the Civil War; war activities of women in Chester, South Carolina in 1862; Henry S. Foote's opinion in 1862 of Bragg's campaign; battle of Chancellorsville; hardships at home; Copperheads; election of Jas. H. Hemphill in 1865 to the South Carolina constitutional convention and the work of that body; movement of James Hemphill's former slaves; bankruptcy of South Carolina in 1865 (James Hemphill was chairman of the finance committee of the senate of that state in 1865); difficulties of Robert Nixon Hemphill in getting freedmen to sign work contracts; hard times in Reconstruction; the Ku Klux Klan activities around Blackstock, South Carolina, in 1871; armed fight between Democrats and Republicans during an election in Kentucky in 1871; the Panic of 1873; Wade Hampton's administration as governor; organization of a militia company in South Carolina; politics of that state in the 1870s; and the state debt of South Carolina.

The papers following the 1870s are largely those of James Calvin Hemphill's career. The latter portion of the collection includes quite a number of letters from William Howard Taft and Daniel H. Chamberlain, both of whom were friends of J.C. Hemphill; from Mrs. Francis W. Dawson I; and from various members of the Hemphill family. There is also a considerable quantity of papers of Robert Reid Hemphill, second son of William Ramsey and Hannah Smith (Lind) Hemphill.

The significant subjects treated in the latter part of the collection are: South Carolina politics in the 1880s; presidential election of 1884; Benjamin R. Tillman and the attitude of Francis W. Dalton I, editor of the Charleston News and Courier before his death in 1888, as well as the attitude of others toward Tillman; the Charleston earthquake of 1886; Theodore Roosevelt; the murder of F.W. Dawson, Sr., in 1888; Hugh S. Thompson's opinion of Roosevelt and Charles Lyman, his fellow members in the Civil Service Commission; illness of Henry W. Grady in 1889; South Carolina politics in the 1890s; colonization of African Americans in Africa; presidential election of 1892; woman suffrage, as part of a bill introduced in the South Carolina senate by Robert Reid Hemphill in 1892; race of John Gary Evans in 1894; presidential campaign of 1896; the Dispensary Law; John L. McLaurin's race for the Senate in 1897; railroads (mentioned occasionally); Gridiron Club; presidential election of 1900; McKinley's "imperialistic policy"; Walter H. Page's opinion of Ellen Glasgow's novel; William McNeill Whistler; Edward W. Blyden's opposition to the miscegenation of black people; establishment of a naval station at Charleston; the South Carolina Inter-State and West Indian Exposition; the appointment of Dr. Crum, an African American, as collector at the port of Charleston; murder of N.G. Gonzales; Joseph Pulitzer's plan to establish a school of journalism at Columbia University; experiences of Robert G. Hemphill as a teacher in Monroe, Georgia; Grover Cleveland; the presidential election of 1904; M. Storey's opposition to Harvard's giving Henry Cabot Lodge an honorary LL.D.; Oswald Garrison Villard; the visit in 1904 by R.W. Gilder with Varina (Howell) Davis; the Ogden Movement; Ludwig Lewishon; , edited by James Calvin Hemphill; Booker T. Washington; race relations in the Mississippi delta in 1905; St. Andrew's Society of Charleston; William L. Hemphill's experiences as an engineer in tin mines in Bolivia; meeting of the Southern Immigration and Industrial Association in Birmingham in 1907; Uncle Joe Cannon's Boot Fund; George Harvey; Joseph Pulitzer; R. Goodwyn Rhett; William Howard Taft; the American Commission to Liberia in 1909; Everett G. Hill's views on Jefferson Davis; the history of Liberia and race relations there; William Jennings Bryan; "yellow journalism"; W.E.B. Dubois; possible U.S. intervention in 1911 in Mexico; Woodrow Wilson; James Cannon, Jr.; Taft's view on the tariff; suit of Ambrose E. Gonzales and J.C. Hemphill vs. D.A. Tompkins, George Stephens, and W.H. Wood; segregation in Balitimore and Washington; prohibition; World War I; League to Enforce Peace; the Alexandria Gazette; Josephus Daniels; the American Motion Picture Corporation; the life of Daniel H. Chamberlain; and John Sharp Williams' description of Key Pittman.

Other papers include invitations and calling cards; other miscellaneous printed material; several boxes of copies of editorials and speeches; and bills and receipts.

The volumes include: a journal (author unknown) of a trip to Europe in 1905; letterbooks running from 1887 to 1903; scrapbooks of newspaper clippings from 1887 to 1916. Several scrapbooks related to James Calvin Hemphill's involvement in the South Carolina Inter-State and West Indian Exposition, the bulk dating from 1901-1902.