The hypothalamic action of progesterone on the regulation of LH secretion was investigated in a rat model ideally suited for the study of progesterone effects under conditions in which the animal is sensitive to progesterone but does not have an estrogen-induced gonadotropin surge. Immature female rats were ovariectomized at 26 days of age and treated for 4 days with a subphysiological dose of 0.1 µg/kg/day estradiol followed by the injection of either 0.8 or 3.2 mg/kg progesterone at 9.30 a.m. on day 5. Serum LH levels were significantly depressed below control and pretreatment values 30 min after either dose of progesterone. At this time, 0.8 mg/kg progesterone administration resulted in a significant increase in MBH-LHRH and plasma LHRH levels. In contrast, the administration of the 3.2 mg/kg dose of progesterone did not result in an increase in MBH-LHRH levels. By 2 p.m., rats receiving 0.8 mg/kg progesterone, but not those receiving 3.2 mg/kg progesterone, showed a significant increase in serum LH concentration and this elevation was maintained at 4 p.m. The increase in serum LH levels was preceded by a rise in MBH-LHRH levels by 1 p.m., followed by a fall at 2 p.m. The LH rise was maintained during the rise and replenishment of the MBH-LHRH by 3 p.m. Between 2 and 3 p.m. the replenishment of MBH-LHRH levels was accompanied by a fall in POA-LHRH levels. These results show that under the proper estrogen priming, and even in the absence of an estrogen-induced gonadotropin surge, a single injection of progesterone can induce changes in hypothalamic LHRH that are similar to those observed on proestrus in the cycling rat, leading to the gonadotropin surge