Alcoholism is three times more prevalent in men than in women. We studied responses of thyrotropin to protirelin (thyrotropin releasing hormone) in nine sons and eight daughters of patients with familial alcoholism and in eight control boys and seven control girls. Basal and protirelin stimulated triiodothyronine, prolactin, and growth hormone concentrations were also measured. The controls were matched for age, sex, and past alcohol exposure with the index children. The sons of familial alcoholics had significantly higher basal thyrotropin levels, peak thyrotropin levels, and thyrotropin areas under the curve than did the control boys. The daughters of patients with familial alcoholism showed no differences from the control girls. Analyses of triiodothyronine, prolactin, and growth hormone concentrations revealed no differences between the index children and controls. We believe that this is the first report of a male-limited neuroendocrine difference between children of alcoholics and control children. Further studies are needed to elucidate the clinical significance of our preliminary findings.