1. 1. The hydroxylated metabolites of amphetamine, p-hydroxyamphetamine ( p-OHA) and p-hydroxynorephedrine ( p-OHN), were administered intracerebroventricularly in mice in order to evaluate their ability to elicit hypothermia. 2. 2. Intracerebroventricular (i.c.v.) administration of p-OHA and p-OHN (1, 3 and 9 μg/mouse) induced maximal hypothermia 30 min after injection. p-OHA and p-OHN (9 μg, i.c.v.) produced maximal decreases in rectal temperature of −6.48 ± 0.44°C and −3.82 ± 0.42°C, respectively. Both metabolites are more effective than amphetamine (at 9 μg, i.c.v., −3.32 ± 0.75°C). 3. 3. Pretreatment with haloperidol (5 μg, i.c.v.) suppressed the fall in temperature produced by p-OHA (3 μg, i.c.v.) and reduced that produced by p-OHN (3 μg, i.c.v.), respectively. The selective dopaminergic D1 receptor antagonist, SCH 23390, and the D2 receptor antagonists, sultopride and metoclopramide, were without effect on the hypothermia induced by either metabolite. Similarly, amphetamine-induced hypothermia was only inhibited by haloperidol. Apomorphine (0.1 mg kg −1, i.p.) did not potentiate the hypothermia induced by either metabolite, whereas the selective dopaminergic D2 agonist, quinpirole (0.2 mg kg −1, i.p.) did. Amphetamine-induced hypothermia was potentiated by apomorphine and quinpirole. 4. 4. Neither the 5-hydroxytryptamine (5-HT) receptor blocker, cyproheptadine, nor the 5-HT receptor agonist, quipazine, modified metabolite-induced hypothermia. In contrast, amphetamine-induced hypothermia was affected by these 5-HT drugs. 5. 5. The neuropeptide CCK-8 (0.04 mg kg −1, i.p.) and γ-butyrolactone (40 mg kg −1, i.p.) potentiated the hypothermia produced by amphetamine and its metabolites. Conversely, desipramine (20 mg kg −1, i.p.) antagonized it. 6. 6. These results show that both hydroxylated metabolites of amphetamine can elicit a strong dose-dependent hypothermia. p-OHA is more potent than p-OHN, which is itself more potent than amphetamine. This potent activity of the metabolites indicates that they play an important role in amphetamine-induced hypothermia. While amphetamine-induced hypothermia involves dopaminergic and 5-hydroxytryptaminergic neurotransmission, metabolite-induced hypothermia is mainly mediated by direct and/or indirect dopaminergic mechanisms, probably by D2 receptor activation.