The possibility that norepinephrine stimulates basal but inhibits TSH-induced thyroid hormone secretion was explored by the use of in vivo and in vitro techniques. Basal thyroid hormone secretion was defined as TSH-independent secretion, experimentally obtained in vivo by pretreatment with T4 or T3. In mice pretreated with 125I and T4, norepinephrine enhanced baseline blood radioiodine levels, but in control mice, norepinephrine failed to alter basal plasma T4 levels. To study whether the stimulated release of radioiodine truly reflects stimulated thyroid hormone secretion, the nature of the radioiodine that was elevated by norepinephrine after 125I pretreatment was investigated. In controls, the fraction of radioiodine that was bound to thyroid hormones was 24.6 +/- 0.8% (+/- SE) of the total radioiodine. This figure increased to 31.9 +/- 1.1% (P less than 0.001) in response to norepinephrine. Further, by a technique of binding the released radioiodine to specific anti-T4 antiserum, norepinephrine was found to increase secretion of radiolabeled T4 by 22 +/- 2% (P less than 0.001). Thus, it is concluded that norepinephrine stimulates basal thyroid hormone secretion in vivo, and that its failure to alter plasma T4 levels is due to the low sensitivity of the technique. In contrast, it was found that norepinephrine inhibits the thyroid stimulatory effect of TSH in vivo. Under in vitro conditions, norepinephrine was found to increase the release of radioiodine that was bound to thyroid hormones from thyroid glands of mice that had been pretreated with 125I. However, norepinephrine failed to alter the baseline thyroid content of cAMP, yet it inhibited the cAMP-accumulating effect of TSH. In conclusion, the present study demonstrates that norepinephrine exerts a dual effect on thyroid hormone secretion in the mouse; it stimulates basal but inhibits TSH-induced thyroid hormone secretion.