We evaluated the participation of nucleus reticularis gigantocellularis (NRGC), a medullary nucleus that plays an important role in the regulation of nociceptive processes, in the antinociceptive effect of angiotensin III (AIII), a biologically active peptide of the renin-angiotensin system. Adult, male Sprague-Dawley rats anesthetized with pentobarbital sodium (40 mg/kg, i.p., with 10 mg/kg/h i.v. infusion supplement) were used. Bilateral, site-specific microinjection of AIII (80 or 160 pmol) into the NRGC produced a dose-related increase in the latency of tail-flick response to noxious thermal stimuli (50 degrees C hot water). Such an antinociceptive action of AIII was blocked by concomitant administration of the AIII receptor antagonist, Ile7-angiotensin III (Ile7-AIII, 10 nmol). At the neuronal level, microiontophoretic application of AIII suppressed, Ile7-AIII reversibly, the responsiveness of nociception-related neurons in the NRGC to tail-clamping. These results demonstrated that central AIII may elicit antinociception via a process that may at least take place at the NRGC.