In rats acutely exposed to cold as compared to room temperature, the toxic responses to parenteral injections of meperidine hydrochloride, of dextroamphetamine sulfate and of prochlorperazine ethanesulfonate were invariably greater in cold than at room temperature. With further experiments an even greater increase was noted in the acute oral toxicity of prochlorperazine dimaleate at 4° C; the acute oral toxicity of this drug was 144 times greater at 4° C than at room temperature. This large difference in toxicity appeared to be an additive effect of the inherent hypothermic action of the drug and of the temperature-lowering action in the cold environment. Tests with larger animals, monkeys and dogs, indicated that the differences in toxicity between the room temperature and cold environments were not as great as in rats. The ability of large animals to retain body heat in the cold for a longer time than rats can may have contributed to the lesser effect. The results with monkeys injected with prochlorperazine in increasing dosage may have revealed the possibility of a tolerance development to the drug. Dextroamphetamine sulfate was about equally effective at either environment in inhibiting sleep in monkeys induced with pentobarbital. The tranquilizing effect of prochlor.perazine, as shown by avoidance behavior in monkeys subjected to a mild electric shock, was found to be about the same at 4° C as at room temperature. In dogs, injections of prochlorperazine at room temperature were about as effective as at 4° C in preventing emesis by an emetic dose of apomorphine.