The effects of inhibition of nitric oxide (NO) synthase in the brain on colonic motor activity were investigated in conscious dogs. Intracerebroventricular (ICV) infusion of N omega-nitro-L-arginine methyl ester (L-NAME) and N omega-nitro-L-arginine (L-NNA) significantly suppressed colonic motor activity. The inhibitory effects occurred 1 h after the end of the infusion and lasted for at least 4 h. This suppression was blocked by a concurrent infusion of L-arginine but not D-arginine. The suppression of colonic motor activity was not blocked by bilateral truncal vagotomy or intravenous administration of phentolamine, an alpha-receptor antagonist, and propranolol, a beta-receptor antagonist. ICV infusion of L-NAME had no significant effect on the occurrence of giant migrating contractions in the colon. By contrast, intravenous administration of L-NAME at higher doses significantly enhanced colonic motor activity. We conclude that the inhibition of NO synthesis in the brain suppresses, whereas the inhibition of NO synthesis in peripheral neurons stimulates, colonic motor activity. The central effect may be mediated by a decrease in cerebral blood flow due to the inhibition of NO synthesis in cerebral arteries.