Intravenous administration of the stimulant drug pipradrol evoked a dose-dependent hyperthermic response in rabbits. This drug effect was significantly reduced by pretreatment with chlorpromazine, phenoxybenzamine, intravenous BE-2254 or intracerebroventricular BE-2254. In animals pretreated with cyproheptadine or atropine, the hyperthermic effect was significantly potentiated. However, haloperidol, pimozide, diphenhydramine and pentobarbital failed to appreciably influence the drug response. These findings suggest that pipradrol-induced hyperthermia in the rabbit involves activation of central alpha-adrenergic receptors and is apparently enhanced by blockade of serotonergic or cholinergic receptors.