The thyroid gland is richly innervated but the effects of activation of these nerves on thyroid hormone secretion are not yet established. In the present study, intravenous injection to mice of 2-deoxy-glucose (2-DG; 60 mumol/animal) was used to activate the autonomic nerves. The nerve activation occurs through the neuroglycopenia. We found that 2-DG inhibited the thyroid-stimulating hormone (TSH; 70 microU/animal)-induced thyroid hormone secretion, measured as release of radioiodine bound to anti-T4 in radioiodine-pretreated mice. This inhibition by 2-DG was completely reversed by the alpha-adrenoceptor antagonist phentolamine but not affected by the beta-adrenoceptor antagonist L-propranolol or the muscarinic receptor antagonist methyl-atropine. It is therefore concluded that neuroglycopenia-induced activation of the autonomic nerves inhibits TSH-induced thyroid hormone secretion by a mechanism that is reversed by phentolamine. It is suggested that it is mainly the adrenergic nerves that are involved in this action, and, consequently, that the function of the adrenergic nerves in thyroid physiology is to restrain the stimulatory action of TSH.