The responsiveness of the hepatic microsomal aryl hydrocarbon hydroxylase (AHH) to testosterone enanthate (TE; 2.5 mumol/kg/day for 9 days) was sex-dependent in adult rats, the enzyme being very resistant to TE in normal adult or ovariectomized females. Administration of testosterone propionate or diethylstilbestrol (1.45 mumol) to neonatal female rats at 1 and 3 days of age did not increase the responsivity to TE in adulthood. However, exposure of female rats to TE (5.0 mumol/kg/day) during the peripubertal period (35-50 days old) resulted in increased sensitivity to TE (+55.2%) when tested in adulthood. The responsivity was further potentiated (+109.3%) if the animals were ovariectomized at 28 days of age. Prepubescent ovariectomized females which received corn oil or estradiol benzoate (1.5 mumol/kg on alternate days) during puberty were not able to respond to TE significantly. These results suggest that the refractoriness of the hepatic AHH to testosterone in adult female rats is determined by the absence of testosterone, as well as the presence of estrogens, during puberty.