Male albino rats, acclimated to 23 °C, were exposed to 2 °C and hypothermia was induced by means of reserpine, chlorpromazine, or noradrenaline. Pretreatment with imipramine, iproniazid, pargyline, or l-triiodothyronine of rats receiving reserpine resulted in better maintenance of metabolic rate and body temperature, and decreased mortality compared with animals receiving reserpine alone. In the case of chlorpromazine and noradrenaline the reverse occurred. Pretreatment with hydrocortisone reduced the hypothermic effect of reserpine, and to a lesser extent that of noradrenaline, but was ineffective with chlorpromazine.The findings are consistent with the hypothesis that noradrenaline is intimately involved with thermogenesis; when tissue stores are depleted, adrenotropic drugs exert a beneficial action but when large amounts of noradrenaline are injected or released endogenously the same drugs increase toxicity. It is suggested that pretreatment with hydrocortisone produces its beneficial effect by altering the pattern of metabolic pathways involved in heat production.