Carbamazepine, a drug that is clinically effective in paroxysmal pain syndromes and in epilepsy, also appears to be effective in the treatment of manic-depressive illness. The mechanisms of action of carbamazepine and its endocrine effects remain unclear. Therefore, the hormone responses to sequential stimuli--namely, arginine, thyrotropin-releasing hormone (TRH), and luteinizing hormone-releasing hormone--were studied in six patients with major depressive disorder before and during treatment with carbamazepine. The drug was found to blunt the thyrotropin-stimulating hormone response to TRH and to augment the prolactin response to arginine. The advantages of the experimental design and the implications of the findings for carbamazepine's mechanism of action in affective illness are discussed.