The expression of neuronal type of nitric oxide synthase (nNOS) has been studied by immunocytochemistry in the brain of rats receiving a single daily (for up to 14 consecutive days) intracerebroventricular (i.c.v.) injection of the HIV-1 recombinant protein gp 120 (100 ng/day). This treatment failed to affect nNOS expression in the cerebral cortex and medial septal nucleus whereas it reduced nNOS immunopositive neurones in the CA1 hippocampal cell layer of rats treated with gp120 for 14 days; the latter effect was accompanied by a parallel decrease in Ca(2+)-dependent NOS enzyme activity in hippocampal brain tissue homogenates. In conclusion, the present data demonstrate that in rats gp120 reduces the expression of nNOS in the hippocampus, an area of the brain involved in memory formation.