1. The effects of two inhibitors of uptake pump in serotonergic neurons, Lilly 110140 and chlorimipramine, on the thermoregulatory responses of unanaesthetized rats to different ambient temperatures (Ta) of 8, 22 and 30 degrees C were assessed. 2. Intraperitoneal administration of either Lilly 110140 or chlorimipramine produced dose-dependent hypothermia at 8 and 22 degrees C Ta. At 8 degrees C Ta the hypothermia was due to a decrease in metabolic heat production. At 22 degrees C Ta, the hypothermia was brought about by both a decrease in metabolic heat production and an increase in cutaneous temperature of the tail and the footsole. 3. However, at 30 degrees C Ta, there were no changes in rectal temperature in response to either Lilly 110140 or chlorimipramine application. 4. The data suggest that an increase in serotonergic receptor activity or in functional serotonin in brain decreases heat production and/or increases heat loss and leads to hypothermia in rats.