The activity of alcohol dehydrogenase is higher in the livers of female rats than that in male rats. Stereotaxic lesions of the anterior periventricular hypothalamus of male rats increased the activity of alcohol dehydrogenase by about 50 percent; larger lesions which destroyed many of the major hypothalamic nuclei increased the enzyme activity 100 percent and abolished the sexual difference in alcohol dehydrogenase activity. The changes in enzyme activity were independent of changes in plasma thyroxine, testosterone and estradiol levels. Hypothalamic lesions in female rats had no effect on the enzyme activity. The sexual difference in alcohol dehydrogenase activity in rats is under hypothalamic control and does not appear to be mediated directly by the plasma level of androgens or estrogens. © 1985.