A plasmid-specified, inducible, but cyclic adenylic acid (cAMP)-independent resistance to chloramphenicol (CM) is reported. The resistance level to CM was increased two- to fourfold by treatment with a small amount of CM for a short period in Escherichia coli strains carrying the R plasmid pJY1, which was obtained from a clinical isolate of Vibrio cholerae. Though cAMP was required for production of CM acetyltransferase (CATase) in cAMP-deficient mutants of E. coli carrying the R100 plasmid, the same species harboring pJY1 did not require cAMP for production of the enzyme. The possibility of a mechanism other than CATase activity for the CM resistance conferred by R plasmids is discussed.