Mice received intraventricular 6-hydroxydopamine (6-OHDA) to deplete brain noradrenaline (NA) and dopamine (DA). 6-OHDA reduced the reaction time of mice to nociceptive stimulus (hot plate) and attenuated the antinociceptive action of oxotremorine. The administration of 6-OHDA to desipramine treated mice prevented both the loss of cerebral NA and the antagonism of oxotremorine's antinociceptive action. The administration of 6-OHDA to pargyline-treated mice increased the depletion of cerebral DA, but the antagonism of oxotremorine's antinociceptive action persisted. Catecholamines were measured in mouse brain at intervals from 1 h to 3 days after administration of 6-OHDA. DA levels failed to correlate with either the reduction in the hot plate reaction time or the antagonism of oxotremorine analgesia, whereas these effects were usually accompanied by a loss of brain NA. Centrally acting DA agonists failed to restore oxotremorine's antinociceptive action in 6-OHDA-treated mice. Intraventricular administration of the acetylcholine synthesis inhibitor triethylcholine to mice did not effect the antinociceptive action of oxotremorine. It is concluded that the antinociceptive action of oxotremorine in mice is initiated by stimulation of muscarinic receptors and involves noradrenergic neurones.