We examined the effect of 60 days of ethanol treatment on protein kinase C (PKC) in membrane and cytosolic fractions of the rat cerebral cortex. Membranal and cytosolic PKC were determined by binding technique using [3H]-phorbol 12,13 dibutyrate (PDBU) as radioligand and phorbol 12-myristate 13-acetate (PMA) as displacer. Chronic ethanol consumption resulted in a decrease in the maximum number of binding sites (Brmmax) of [3H]-PDBU binding to membranal PKC without significant change in the apparent dissociation constant (KrmD) in the rat cortex. We also observed that chronic ethanol consumption had no significant effect on Brmmax or KrmD of [3H]-PDBU binding to cytosolic PKC in the rat cerebral cortex. These results suggest that chronic ethanol consumption leads to the down-regulation of brain PKC associated with membrane but not with cytosol. © 1993.