3H-Phorbol 12,13 dibutyrate binding to rat brain was modified by chronic ethanol treatment. Among the areas examined hippocampus and cortex showed a decrease in Bmax values of 32 and 24% respectively. No significant effect was observed in hypothalamus and cerebellum. In vitro ethanol did not modify the binding in all the areas except at molar concentrations. In hippocampus and cortex the direct measurement of protein kinase C activity indicated that the decrease in phorbol ester binding was accompanied with a concomitant decrease in kinase activity. The results indicate that chronic ethanol treatment leads to an inhibition of brain protein kinase C function.