The basal and isoproterenol stimulated levels of cyclic AMP in NIH3T3 and H- ras transformed NIH3T3 cells were equivalent. In exponentially growing cells, the phorbol ester 12-O-tetradecanoyl-13-acetate (TAP) inhibited the β-adrenergic response of NIH3T3 cells, but not of the ras -transformed line. Another line of NIH3T3 cells transformed by a non- ras gene exhibited the normal loss of β-adrenergic response by the tumor promoter. These results are consistent with a role for p21 in signal transduction related to the effects of TPA.