A reduced thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) has been reported in both alcoholic and depressed men. To discern whether the pathophysiological basis of a reduced TSH response is similar in these two disorders, the present study compares the dose-response patterns of TSH and prolactin (PRL) to TRH in depressed, alcoholic, and control men. Four doses of TRH (25, 100, 500, and 800 micrograms) were given at several day intervals to 6 men with major depression, 8 men with alcohol dependence, and 7 control men. Examination of the pattern of TRH-induced TSH and PRL response revealed differences for each paired group comparison: depressed versus control, depressed versus alcoholic, and alcoholic versus control. Compared with controls, depressed men had low TSH and low PRL responses to TRH, whereas alcoholic men had low TSH responses and normal PRL responses. Levels of neither thyroid hormones, cortisol, or sex steroids, nor age or body size, explained these differences. These findings suggest that the pathophysiological basis of a reduced TSH response to TRH is different in alcoholism, compared with depression.