The effect of delta 9-tetrahydrocannabinol (delta 9-THC) on body temperature of the mouse was studied. A dose-response relationship (5-100 mg/kg) for the hypothermic effect of delta 9-THC was seen. The investigation as to the mechanism underlying the hypothermic action of delta 9-THC was also investigated. The relatively specific dopamine antagonist haloperidol potentiated delta 9-THC-induced hypothermia as did the alpha-adrenoceptor antagonist phenoxybenzamine. However, depletion of serotonin with P-chlorophenylalanine reduced the hypothermic response to delta 9-THC as did pretreatment with the serotonin antagonist methysergide. Inhibition of re-uptake of serotonin with clomipramine potentiated the hypothermia following delta 9-THC. It is suggested that the hypothermic effect of delta 9-THC in the mouse is mediated to a large extent via serotonergic mechanisms.