The effects of gambiertoxin (CTX-4B), purified from the dinoflagellate Gambierdiscus toxicus, were assessed on the morphology of both frog myelinated axons and motor nerve terminals, using confocal laser scanning microscopy. During the action of the toxin (24 and 30 nM), a marked swelling of nodes of Ranvier and motor nerve terminals was observed. The CTX-4B-induced swelling could be prevented by blocking voltage-dependent Na+ channels with tetrodotoxin, and could be partly reversed by an external hyperosmotic solution containing 100 mM D-mannitol. The results suggest that CTX-4B, by modifying voltage-dependent Na+ channels, increases internal Na+ concentration of axons and nerve terminals and consequently induces water influx to compensate such an increase. It is suggested that stimulated transmitter release by CTX-4B, as well as by hyperosmotic dmannitol, contribute also to the swelling of the terminals through an increase in their surface area.