Nuclear factor kappa B (NF-kappa B) is a DNA-binding regulatory factor that controls the transcription of a number of genes. Various agents are known to activate this factor. We have studied the ability of cAMP to stimulate NF-kappa B activity in human myeloid cells. Electrophoretic mobility assay revealed that structural cAMP analogs and agents elevating intracellular cAMP levels induced NF-kappa B DNA-binding activity. The inducibility was dependent on the maturation stage of myeloid cells. In promyelocytic HL-60 cells cAMP induced higher NF-kappa B activity than in more differential THP-1 cells and in human monocytes. By transfecting HL-60 and THP-1 cells with reporter constructs containing NF-kappa B DNA-binding sites, we observed that cAMP-induced NF-kappa B was transcriptionally active.