The regulation of T-cell antigen receptor (TcR) gene expression by phorbol ester and cAMP was studied in human thymocytes. Incubation of human thymocytes in the presence of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate increased the levels of the mRNAs of TcR-alpha and -delta while the levels of TcR-beta and -gamma mRNA were not affected. cAMP, on the other hand, caused a decrease in TcR-alpha and -delta mRNA levels but also did not affect TcR-beta and -gamma mRNA levels. The induction of TcR-alpha and -delta mRNA by 12-O-tetradecanoylphorbol-13-acetate occurred at the transcriptional level only whereas cAMP treatment decreased both TcR-alpha gene transcription and the stability of its mRNA. The similarity in the transcriptional control of TcR-alpha and -delta genes combined with their close chromosomal location raises the possibility that they share common DNA regulatory elements.