In a 2-part study 15 female baboons were injected with 100 mcg luteinizing hormone-releasing hormone (LH-RH) sc in the early follicular and early luteal phases to examine the mechanism of LH release. Assays of blood samples after the luteal-phase injection showed a peak plasma level of LH-RH at 4 minutes with a sharp then slow decline. LH peaked within 30 minutes and again at 90 and 150 minutes the latter 2 peaks not apparently related to the LH-RH injection. There was a lesser LH release after the follicular-phase injection. Since elevations of plasma estrogen and progestin were observed within 45 minutes in both treated animals and controls it was hypothesized that the later LH peaks might be due to enhancement of the response to LH-RH by the estrogen and progestin. Injections of 600 mcg estradiol benzoate or 10 mg progesterone for 3 days enhanced pituitary LH responsiveness but the injection of both together showed no significant effect. It is suggested that estrogen and progesterone may exert both a direct effect on the hypothalamus to control LH-RH secretion and an effect on the pituitary gonadotropins to alter the sensitivity to this LH-RH secretion.