The effect of maturation, castration, and sex hormonal treatment on hepatic xanthine oxidase activity (XOA) was evaluated in Sprague-Dawley rats. In mature rats XOA was 59% greater in males than in females, whereas in the immature animal the differences between sexes were insignificant. Pubescence resulted in a twofold increase in activity in the male which was prevented by prepubertal orchiectomy. Conversely, prepubertal oophorectomy caused a twofold increase in XOA in females. Urinary uric acid excretion paralleled XOA in rats fed 1% oxonic acid. XOA was significantly elevated in females after postpubertal castration or testosterone treatment while orchiectomy or estradiol-17 beta treatment in the mature male showed no effect. In summary, these data suggest that androgens are required during puberty for full expression of hepatic XOA, and furthermore, an ovarian suppressive effect is evident. In the adult rat only the female responds appreciably to hormonal manipulation.