The objective of this study was to determine whether progesterone prevents the stimulatory effects of oestradiol on GnRH receptor gene expression. In Expt 1, ewes were treated during the luteal phase (days 10-12 of the oestrous cycle) with either one or five subcutaneous implants containing oestradiol (n = 6 per group). Control ewes received no treatment (n = 6). Anterior pituitary glands were collected 16 h after treatment with oestradiol. Steady-state amounts of GnRH receptor mRNA were similar among all three treatment groups despite increased circulating concentrations of oestradiol in implanted ewes at the time of pituitary collection (4.3 +/- 0.6 and 24.7 +/- 2.6 pg ml-1 in ewes treated with one or five implants, respectively, compared with 0.5 pg ml-1 in controls). Experiment 2 was designed to determine whether progesterone was the ovarian factor preventing the stimulatory effects of oestradiol on expression of the GnRH receptor gene in Expt 1. Twenty-five ewes were ovariectomized on day 6 or day 7 of the oestrous cycle and assigned to one of five treatment groups (n = 5 per group). Control ewes received no further treatment. Endogenous luteal phase concentrations of progesterone were replaced in three groups of ewes at the time of ovariectomy via intravaginal implants. Three days after ovariectomy, one group of progesterone-treated ewes received one oestradiol implant, while another group of progesterone-treated ewes received five oestradiol implants. An additional group was treated with five oestradiol implants only, and anterior pituitary glands were collected from all ewes 16 h later. Compared with untreated ovariectomized ewes, treatment with progesterone alone did not affect amounts of GnRH receptor mRNA. In ewes treated with progesterone and either one or five oestradiol implants, steady-state amounts of GnRH receptor mRNA were increased twofold (P < 0.01). Treatment with oestradiol in the absence of progesterone increased amounts of GnRH receptor mRNA threefold (P < 0.001). These results provide evidence that the stimulatory effects of oestradiol on the expression of the GnRH receptor gene are prevented during the natural luteal phase in ewes. However, progesterone does not appear to act independently to mediate this effect.