Ascending noradrenergic and serotonergic pathways were lesioned by injection of 6-hydroxydopamine into the dorsal bundle or 5,7-dihydroxytryptamine into the ventromedial tegmentum respectively, and the antinociceptive effect of morphine, administered by intracerebroventricular injection assessed using the tail-flick test 3-14 days later. Lesions of the dorsal bundle selectively depleted levels of noradrenaline (NA) in the forebrain and increased the antinociceptive effect of morphine early, but not later, in the time course of action. Lesions to the locus coeruleus depleted NA in the forebrain and spinal cord but had no effect on the antinociceptive action of morphine. Lesions of the ventromedial tegmentum selectively depleted 5-hydroxytryptamine (5-HT) in the forebrain and transiently reduced the action of morphine. 5,7-Dihydroxytryptamine given intraventricularly depleted 5-HT in the forebrain and spinal cord and also transiently reduced the antinociceptive effect of morphine. These results indicate that aminergic pathways, projecting to the forebrain, are involved in the suppression of the tail-flick reflex produced by injection of morphine into the lateral ventricle.