In order to evaluate a possible role of brain nitric oxide (NO) on the control of penile erection, the effect of nitroglycerin, that is thought to act by producing NO, was studied on spontaneous penile erection in male rats. In addition the effect of drugs that prevent NO formation and/or activity such as N-G-nitro-L-arginine methyl ester (NAME) and methylene blue, on N-methyl-D-aspartic acid (NMDA)-, apomorphine- and oxytocin-induced penile erection was also studied. Nitroglycerin induced penile erection in a dose-dependent manner when given intracerebroventricularly (i.c.v.) (33-99 mu g) or in the paraventricular nucleus of the hypothalamus (0.8-3.3 mu g). Nitroglycerin-induced penile erection was prevented by the guanylate cyclase inhibitor methylene blue injected i.c.v. (20-400 mu g) but not in the paraventricular nucleus of the hypothalamus (10-20 mu g). Conversely, NMDA-, apomorphine- and oxytocin-induced penile erection was prevented by NAME (150 mu g) or methylene blue (400 mu g) given i.c.v. NAME (20 mu g), but not methylene blue (20 mu g), was effective in preventing the behavioral response also when injected in the paraventricular nucleus. The present results suggest that NO is a common mediator of several neurotransmitters involved in the control of this primary male sexual function.