This study was performed to determine if two sex differences in gonadotropin responses to negative feedback, the acute postcastration rise and the effect of follicular fluid (FF) in the acute castrate, could be reversed by neonatal treatment with sex-opposite steroids. Female rats that received testosterone propionate (TP-females) and male rats that received estradiol benzoate (EB-males) neonatally were studied as adults. EB-males showed an LH response to gonadectomy which was much less than control males, and did not differ from control females, which could suggest the hypothesis that neonatal estrogen 'feminizes' the male response to gonadectomy. However, as the postgonadectomy response in both LH and FSH was depressed in both TP-females and EB-males in comparison to their respective matched sex controls, neonatal steroid treatment appears simply to impair hypothalamic-pituitary function. This is not a result of decreased pituitary responsiveness to GnRH in TP-females and EB-males. On the other hand, neonatal steroid treatment does not change the sex-specific response to imposition of peptide negative feedback (i.e., FF administration). In control and TP-females, FF significantly suppressed serum FSH levels, both in intact animals and 9 h after gonadectomy. In both control and EB-males, FF suppressed FSH in intact animals, but failed to do so in acute castrates. Thus, neonatal steroid treatment does not reverse the sex differences in gonadal-gonadotropin interrelations, but rather causes an impairment in the acute recognition of loss of negative feedback at the hypothalamic level.