Canatoxin (CNTX), a neurotoxic protein, is known to activate platelet secretion and aggregation in vitro through a lipoxygenase-dependent pathway. This study shows that CNTX also induces time and dose-dependent serotonin secretion from rat brain synaptosomes. The secretory effect induced by 6 microM CNTX was similar to that elicited by 150 mM KCl. Nordihydroguaiaretic acid (500 microM) completely abolished CNTX-induced serotonin release while 150 microM indomethacin had no effect. These data suggest the involvement of the lipoxygenase pathway in neurotransmitter release elicited by CNTX as occurs in the platelet.