In vivo administration of TCDD produces an increase in the level of Protein Kinase C in the hepatic plasma membrane. We have studied the direct effects of TCDD on cultured EL4 thymoma cells, which contain a large amount of Protein Kinase C and respond to phorbol esters with rapid translocation of the kinase to the membrane, followed by growth inhibition, adherence to substrate and production of interleukin 2. TCDD (10-1000 nM) did not compete with 3H-phorbol dibutyrate for binding to cytosolic Protein Kinase C, and had no effect on Protein Kinase C activity in vitro. TCDD did not stimulate translocation of Protein Kinase C to the membrane, and did not affect phorbol ester-stimulated translocation. TCDD did not inhibit EL4 cell growth or affect phorbol ester induced growth inhibition, and failed to stimulate production of interleukin 2. Thus, TCDD does not appear to activate Protein Kinase C in EL4 cells.