The beta-adrenergic agonist isoproterenol (100-200 mug/kg body wt sc) induces vasodilation and an increase in skin temperature of the tail of the euthyroid but not the hypothyroid rat. Administration of thyroxine (25 mug/kg body wt per day) to rats made hypothyroid by means of the antithyroid drug aminotriazole (0.5 g/kg of foof) returned responsiveness to control level. Reduced responsiveness to isoproterenol occurred between 1 and 5 wk of treatment with aminotriazole. Increase in tail skin temperature induced in euthyroid rats by isoproterenol was blocked by administration of propranolol (7.5 mg/kg ip). Other beta-adrenergic-induced responses, including increased water intake and increased plasma glucose concentration, also were reduced in hypothyroid rats and returned to control level by administration of thyroxine. Thus, hypothyroidism appears to be accompanied by a reduced beta-adrenergic responsiveness as assessed by changes in tail skin temperature, water intake, and plasma glucose concentration after injection of isoproterenol. Since administration of thyroxine returned the responses of hypothyroid rats to control levels, it appears that thyroxine is important in maintaining beta-adrenergic responsiveness under these conditions.