Effect of methylmercury chloride (MMC) on behavior was studied in male ICR-JCL mice. In order to clarify the causal relationship between the potent suppressing action of MMC on the central cholinergic system and toxic manifestations, behavioral changes induced by MMC were compared with those induced by the two reference drugs, hemicholinium-3 (HC-3) and 3'-chloro-4-stilbazole (CS; a potent choline acetyltransferase inhibitor). When administered intraperitoneally, daily in a dose of 5 mg Hg/kg/day, MMC caused a decrease in spontaneous motor activity, rotarod dysfunction, and hypothermia before an abrupt loss in body weight and the appearance of overt signs. These behavioral changes were similar to some extent to those induced by HC-3 or CS. A single intracerebral injection of HC-3 (51 or 100 micrograms/kg) caused hypothermia and rotarod dysfunction over a period of 40-250 min. A single intraperitoneal administration of CS (100 or 200 mg/kg) induced a decrease in spontaneous motor activity, hypothermia, and rotarod dysfunction over a period of 1-5 hours after injection. These results suggest that the prior toxic behavioral changes caused by MMC may be related to suppression of the cholinergic system.