The participation of circulating growth hormone (GH) as a regulator of sex differences in hepatic aldehyde oxidase (AO) activity in ddy mice was examined. The 2- to 3-fold higher activities in adult male mice compared with adult female mice were decreased to the female levels by neonatal pretreatment with monosodium glutamate (MSG) or monosodium aspartate (MSA), either of which is known to reduce circulating GH levels. A decline of the activities in the MSG-treated male mice was restored nearly to the male control levels by subsequent injections of human GH every 12 hr for 7 days. These changes in AO activities in male mice caused by the excitotoxic amino acids were not observed in females. Hypophysectomy markedly decreased hepatic AO activities in male mice and partially in female mice. The activities in hypophysectomized male mice were restored again to levels similar to the control males by intermittent injections of human GH. Administration of testosterone propionate (TP) significantly increased the activities of hepatic AO in intact female mice, but not in MSA-treated or hypophysectomized females. On the other hand, the AO activities in adult male mice were decreased partially by the administration of estradiol benzoate. These results indicate that the pituitary GH is involved as one of the major regulatory factors of sex differences in the activities of hepatic AO in mice and TP also contributes to maintaining the higher activity in male mice mainly through the hypothalamus-pituitary system.