The role of adrenergic receptors in regulation of rat thymus type II thyroxine 5'-deiodinase (5'-D) activity was investigated. Our results show that norepinephrine, an alpha- and beta-adrenergic agonist elicited an increase in thymus 5'-D activity. Isoproterenol, beta-adrenergic agonist, also increased the enzyme activity, being less effective than norepinephrine. Moreover, alpha-adrenergic agonists, i.e., methoxamine, an alpha1-agonist, and clonidine, an alpha2-agonist, did not increase 5'-D activity. The effect of isoproterenol was potentiated by methoxamine, but the potentiating effect was observed only at doses of isoproterenol which induce submaximal activation of the enzyme. Administration of propranolol, beta-adrenergic blocker, and prazosin, an alpha1-adrenergic blocker, inhibited significantly the activation of the enzyme induced by norepinephrine. However, yohimbine, an alpha2-adrenergic blocker, had small effect. These results show, in hypothyroid rats, a clear regulation by adrenergic mechanisms of 5'-D activity in the thymus, where alpha- and beta-adrenergic receptors might be involved.