In 1978, Pickering sought the Republican nomination for the United States Senate seat being vacated by veteran Democrat James O. Eastland, but he lost his party's nomination to U.S. Representative Thad Cochran of Mississippi's 4th congressional district. Cochran won in a three-way general election against Democrat Maurice Dantin and Independent]] Charles Evers, a well-known figure in the civil rights movement. In 1979 Pickering ran for state attorney general, but he lost to Democrat and later governor, William Allain. He ran on the ticket headed for the second consecutive time by the GOP gubernatorial nominee, businessman Gil Carmichael. From 1976 to 1978, Pickering was the chairman of the Mississippi Republican Party, having succeeded Clarke Reed.