Endogenous opioid peptides (EOPs) suppress pulsatile LH release during pregnancy in the rat, but the stimulatory effect of the EOP receptor antagonist naloxone on LH pulse frequency is reduced or eliminated on day 22 of gestation [13]. Plasma progesterone (P) levels are elevated through day 20 and fall by day 22. The aim of this study was to determine whether the decline in plasma P levels underlies the loss of EOP suppression of LH pulse frequency on day 22. Rats were bled on day 20 of pregnancy while being infused with 0.9% saline (0.5 ml/h) for 3 h, or implanted with empty or P-filled silastic capsules on day 20 and bled on day 22 while being infused first with saline for 3 h and then naloxone (0.5 mg/kg/h) for 3 h. Plasma P levels in the P-capsule group did not differ significantly from day 20 values, whereas P values in the empty capsule group were markedly decreased compared to day 20 levels and to values in the P-capsule group. Plasma estradiol values did not vary significantly between the two capsule-implanted groups. Mean blood LH levels increased between day 20 and day 22 due to an increase in LH pulse frequency and a small but significant increase in LH pulse amplitude. On day 22, mean blood LH levels, pulse amplitude and pulse frequency values during the saline infusion period in the P-capsule group were less than in the empty capsule group, and did not differ from values in the day 20 group. Naloxone infusion increased mean blood LH levels and pulse amplitude in both the empty and the P-capsule groups. However, no increase in LH pulse frequency was observed in the empty capsule group in response to naloxone infusion, whereas pulse frequency during naloxone infusion in the P-capsule group increased markedly. In another study, pituitary responsiveness to LHRH was measured during saline infusion on day 22 and was greater in rats bearing empty than P-filled silastic capsules. Since the stimulatory effect of naloxone on LH pulse frequency was only seen in the P-capsule group, which had the lowest LH response to LHRH, this rules out the possibility that low pituitary responsiveness to LHRH on day 22 contributed to the reduced effectiveness of naloxone in increasing LH pulse frequency at this time. Overall, the data suggest that as P levels decline rapidly on day 22, P-dependent EOP suppression of LH pulse frequency is diminished, allowing an increase in this parameter of pulsatile LH secretion, and eliminating the stimulatory effect of naloxone on pulse frequency. In contrast, naloxone was able to stimulate LH pulse amplitude in both capsule-implanted groups, indicating that EOP suppression of pulse amplitude is not dependent on the presence of high plasma P levels and is still active at the end of gestation in the rat.