Chlorpromazine-and haloperidol-induced hypothermia were examined in mice. The α₁ receptor agonist phenylephrine partially antagonized the hypothermia, while the dopamine D₂ receptor agonist apomorphine did not inhibit it. The central serotonin₂ (5-HT₂) receptor agonist 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) strongly inhibited the chlorpromazine-and haloperidol-induced hypothermia. Both drugs at doses which can elicit hypothermia antagonized head twitch responses mediated by the central 5-HT₂ receptor. These results suggest that the chlorpromazine-and haloperidol-induced hypothermia may be mediated by the blockade of the central 5-HT₂ receptor.