Hypophysectomy of male animals has little effect on the hepatic androst-4-ene,3,17-dione (androstenedione) metabolism, except for possible changes in the kinetics of the 16alpha-and 7alpha-hydroxylases. On the other hand, hypophysectomy of female animals leads to a "masculinization" of hepatic androstenedione metabolism, following the changes seen in Vmax. of the enzymes involved, probably due to the removal of the source of "feminizing factor" thought to maintain the "female" type of metabolism in the liver. There seems to be a temporal dissociation of the effects on the various enzymes, indicating different cellular control mechanisms for these enzymes. Oestrogen treatment of male rats causes "feminization" of the hepatic androstenedione metabolism. The time study shows an initial increase in 17-hydroxy steroid oxidoreductase and 6beta- and 16alpha-hydroxylase activities, followed by a decrease to the values in females. This biphasic effect is possibly due to an initial direct effect via the hypothalamo-pituitary system.