The rate of reduction of the [DELTA]4-graiping of the adreno-cortical steroid 11-deoxycortisol was 3-4 fold greater in female than in male rat liver whole homogenates whether expressed in terms of tissue wet weight equivalents or mg of total N used. The same sex difference was found in microsomal fractions containing the [DELTA]4-5[alpha]-hydrogenase. Evidence was found for only one [DELTA]4^-hydrogenase (5[alpha]- microsomal) in female rat liver in contrast to the male liver which contains the soluble [DELTA]4-5[beta]-hydrogenase as well. Ovariectomy of adult female rats did not produce any marked change in enzyme titer whereas hypophysectomy resulted in a sharp drop (73%), which could be reversed in part by ACTH, growth hormone or pregnant mare''s serum.