The human immunodeficiency virus type 1 (HIV-1) coat glycoprotein, GP120 has been reported to cause death of several neuronal cell types maintained in vitro. In the present experiments the gross behavioural, electrocortical (ECoG) and neuropathological effects of GP120 were studied in rats chronically microinfused into one lateral cerebral ventricle (i.c.v.) via mini-osmotic pumps. Treatment with GP120 (100 ng/day) for 1, 7 and 14 consecutive days lacked postural, motor and ECoG effects nor did it produce any apparent brain damage. In addition, acute i.c.v. injection of a subconvulsive dose (500 ng) of N-methyl-D-aspartate (NMDA) did not produce motor and ECoG epileptogenic discharges in rats which received 1 h beforehand a dose of GP120 (900 ng) into the dorsal hippocampus ipsilateral to the injected ventricle; per se this dose of GP120 was ineffective. In conclusion, the present experiments demonstrate that acute or chronic microinfusion of GP120 into the rat cerebral ventricular system does not produce neurotoxic effects. In addition, they demonstrate that intrahippocampal GP120 does not sensitize rats to the excitotoxic effects of a subconvulsive dose of NMDA.