The effect of NG-nitro-L-arginine methylester (NAME) and N-mono-methyl-L-arginine (NMMA), inhibitors of nitric oxide (NO) synthase on penile erection and yawning induced by N-methyl-D-aspartic acid (NMDA) injected in the paraventricular nucleus of the hypothalamus (PVN) was studied in male rats. NAME (75-150 micrograms) and NMMA (250-500 micrograms), but not N-monomethyl-D-arginine (D-NMMA)(250-500 micrograms) prevented both responses in a dose-dependent manner when given intracerebroventricularly (i.c.v.) 15 min before NMDA (50 ng). NMDA-induced penile erection and yawning was also prevented by the guanylate cyclase inhibitor methylene blue (200-400 micrograms i.c.v.), but not by the NO scavenger methemoglobin (50-100 micrograms i.c.v.). NAME (10-20 micrograms), but not Methylene blue or methemoglobin (10-20 micrograms), prevented NMDA-induced responses also when injected in the PVN 15 min before NMDA. The present results suggest that NMDA-induced penile erection and yawning is mediated by an increased NO synthesis in the PVN.