The purpose of the present study was to determine if gonadal steroids can alter the amounts of GnRH receptor mRNA in the pyramidal and granule neurons of the hippocampus of female and male rats and if GnRH causes a change in the production of inositol phosphates in hippocampal slices in vitro. The results show that in the ovariectomized rat the amount of GnRH receptor mRNA is increased to 137% in area CA1 and to 147% in area CA3 and in the dentate gyrus when compared to the ovariectomized, estradiol-progesterone treated animal. Similarly, in the orchidectomized male rat the amount of GnRH receptor mRNA is increased to 155% in area CA1, to 146% in area CA3 and to 145% in the dentate gyrus when compared to the intact male rat. There was no significant difference in the relative amounts of GnRH receptor mRNA when gonadectomized male and female rats were compared. Addition of GnRH (100 pM-1 microM) to hippocampal slices in vitro caused a dose-dependent increase in the production of [3H]inositol phosphate which was abolished by co-administration of a GnRH antagonist. The increase in inositol phosphate production was significantly higher at low doses of GnRH (100 pM-1 nM) in estradiol-progesterone treated female and in intact male rats when compared to gonadectomized rats. The results suggest that the amount of GnRH receptor mRNA in the hippocampus is at least in part regulated by gonadal steroids and that the steroid hormones can sensitize the GnRH target neurons to respond more robustly to a GnRH stimulus.