Abstract The present study investigated a potential role for cannabinoid CB 1 and CB 2 receptors in capsaicin-evoked hypothermia. Capsaicin (1 mg/kg, s.c.) caused rapid and significant hypothermia in rats. Pretreatment with SR 141716A (1, 2.5 and 5 mg/kg, i.p.), a CB 1 antagonist, or SR 144528 (1, 2.5 and 5 mg/kg, i.p.), a CB 2 antagonist, did not affect capsaicin-induced hypothermia. In separate experiments, the hypothermia caused by WIN 55212-2 (5 mg/kg, i.m.), a cannabinoid agonist, was not significantly altered by capsazepine (10 and 30 mg/kg, i.p.) or SB 366791 (2 mg/kg, i.p.), a novel TRPV1 antagonist. These data suggest that capsaicin causes hypothermia by a CB 1- and CB 2-independent mechanism, and that WIN 55212-2 causes hypothermia by a TRPV1-independent mechanism.