Simultaneous application of cyclosporine A (CsA) and the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on mouse skin strongly inhibits various biological responses to TPA. Delayed application of CsA is less effective. CsA given 1-2 h after TPA is unable to suppress TPA effects. Thus, the process that can be inhibited by CsA and that appears to be crucial for the response to TPA occurs rather early in TPA action.