The protein kinase C activator 4 beta-phorbol 12,13-dibutyrate (PDB) enhanced in a concentration-dependent manner the electrically stimulated release of [3H]noradrenaline ([3H]NA) and [3H]dopamine ([3H]DA) from rat amygdala slices in vitro. PDB enhanced the basal release of [3H]NA and [3H]DA as well. 4 alpha-Phorbol 12,13-didecanoate, which lacks the capacity to activate protein kinase C, was without effect on either basal or electrically stimulated release of [3H]NA and [3H]DA. Polymyxin B, which is a relatively selective protein kinase C inhibitor, decreased in a concentration-dependent manner the electrically stimulated release of both [3H]NA and [3H]DA from amygdala slices, whereas it enhanced the basal release of both neuromessengers. In the presence of 1.5 X 10(-7) M PDB, a concentration which when added to the superfusion medium alone doubled the electrically stimulated release of both [3H]NA and [3H]DA, polymyxin B again decreased in a concentration-dependent manner the release of both neuromessengers. At all polymyxin B concentrations used, the effect of the PKC inhibitor, expressed as percent inhibition, in the presence of PDB was approximately the same as that observed in the absence of PDB. This suggests that the antagonism between PDB and polymyxin B at the level of protein kinase C is not a competitive one. The effects of PDB and polymyxin B on basal release were additive. Taken together, these data suggest that in the amygdala presynaptically localized protein kinase C plays a role in signal transduction processes related to the exocytotic secretion of NA and DA from their nerve terminals.