Sexually dimorphic regulation of phenobarbital-induced cytochromes P450 2B1 and 2B2 (collectively referred to as P450 2B) as well as P450 2B-dependent monooxygenase activities was studied in multi-hormone-depleted hypophysectomized rats and in growth hormone (GH)-deficient monosodium glutamate (MSG)-treated rats. Our results indicate that endogenous GH suppresses phenobarbital induction of P450 2B and that the feminine pattern of continuous GH secretion is more suppressive than the masculine profile of episodic secretion. Moreover, we have found that it is the height of the GH pulse, and not necessarily its frequency nor the interpulse trough periods, that signals the suppressive effects of GH on P450 2B expression in male rats. Last, irrespective of the presence or absence of circulating GH, the magnitude of phenobarbital induction of P450 2B and associated monooxygenases was consistently lower in female rats, suggesting the presence of some degree of sex-dependent, but GH-independent regulation.