Abstract-In order to clarify the mechanism of the different sensitivity of the adren oceptors between normal and hypothyroid rats, cyclic AMP levels in the liver and heart were measured after the administration of phenylephrine, isoproterenol, epine phrine and methoxamine.Cyclic AMP increased in all cases, but the extent of its increment in the heart was much less than that in the liver. Phentolamine and pro pranolol showed only a partial inhibition of cyclic AMP elevation by the agonists in the liver from normal and hypothyroid rat. On the other hand, propranolol blocked completely the effect of the agonists on the heart from both groups. It was also ob served that cyclic AMP increased in adrenalectomized rats after the injection of the adrenergic agonists. The basal activity of protein kinase in hypothyroid status was slightly lower than that in the normal, but this enzyme was stimulated in the presence of cyclic AMP in vitro. These results suggest that the function of F3-adrenoceptor remained normal even in hypothyroidism and responded well to isoproterenol and epinephrine.It is also indicated that the increased sensitivity of a-adrenoceptor to phenylephrine in the hypothyroid atria previously observed is probably in part inde pendent of the mechanism mediated by cyclic AMP.It is well known that the effects of catecholamines on several tissues are mediated by intracellular cyclic AMP (1) and also regulated by thyroid status (2).In previous studies we have shown the increased sensitivity of a-adrenoceptor in the atria of hypothyroid rats and the reduced sensitivity of Q-adrenoceptor in the atria and the liver of the same animals (3-7). Namely, positive inotropic and chronotropic responses of the rat atria to phenylephrine were increased in hypothyroid status. On the other hand, the stimulative effect of isoproterenol on the atria was reduced under that condition. Fur thermore, increased gluconeogenesis from lactate could still be observed in the hypothyroid liver by the administration of phenylephrine, whereas that effect of isoproterenol disappeared.In order to clarify whether or not these phenomena in hypothyroid status are dependent on changes in levels of cyclic AMP, these levels in the liver and heart were determined after the injection of the adrenergic agonists. Protein kinase activity was also determined in these tissues.