The protein kinase C activator phorbol 12-myristate 13-acetate (TPA) augments the level of cytoplasmic mRNA for cytoskeletal actin and the beta chain of the T cell antigen receptor (TCR beta) in peripheral blood lymphocytes. Calcium ionophore A23187 has an antagonistic effect on these increases. The immunosuppressive drug cyclosporin A blocked both positive and negative effects of A23187 without affecting those of TPA. TPA-mediated increases in cytoplasmic RNA for both genes can occur when transcription is blocked with actinomycin D and no increase is observed in the corresponding total cellular RNA. Activation of protein kinase C can thus mediate the accumulation of these mRNAs by a post-transcriptional mechanism.