New World scorpion venom contains protein toxins specific for ion channels in the plasmalemma of excitable cells. The effects were examined of whole venoms from Tityus serrulatus, T. bahiensis and T. stigmurus, and some purified toxins in isolated nerve endings (synaptosomes) and pancreatic acinar cells. Both systems initiated exocytosis in a dose-dependent response to the venom or its bioactive protein toxins. Actions differed, however, such that pancreatic acinar cells required Ca2+ while cerebrocortical synaptosomes responded by a Ca(2+)-dependent mechanism, except in the case of one toxin, IV-5, that elicited a Ca(2+)-independent response. Membrane depolarization caused by scorpion venom toxins was measured via radioisotopic discharge of tetra[3H]phenylphosphonium bromide. The role of protein kinase C in second-messenger coupling in pancreatic acinar cells is favored over ion-exclusive routes characteristic of synaptosomes.