This study was designed to evaluate the role of luteinizing hormone (LH) and prolactin (PRL) in regulating pulsatile progesterone secretion in the human. This was done first by correlating the frequency of progesterone, LH and PRL pulses during the mid-luteal phase of normal cycles. Second, by increasing the frequency of LH pulses with naloxone and GnRH injections and examining the impact on progesterone pulse frequency. Third, by abolishing PRL pulsatility with metoclopramide and looking at the effect on progesterone pulsatility. Nine normal subjects in the mid-luteal phase (4-10 days after the initial postovulatory rise in progesterone) were studied for 8 h with blood samples taken at 15 min intervals. Each sample was assayed for progesterone, LH and PRL and the pulse frequency (number of pulses in 8 h) determined for each hormone. The mean pulse frequencies were 2.3 (s.e.m. = 0.4) for progesterone, 1.3 (s.e.m. = 0.4) for LH, and 2.1 (s.e.m. = 0.3) for PRL. Cross-correlation analysis showed that there was no significant synchrony between pulses of progesterone and pulses of LH and PRL. When naloxone was given to six normal subjects in the mid-luteal phase, the mean LH pulse frequency (number of pulses in 6 h) was increased from 2.2 (s.e.m. = 0.3) during a saline infusion to 3.2 (s.e.m. = 0.5) during the naloxone infusion (P less than 0.05). However, the mean pulse frequency for progesterone remained unchanged during the saline and naloxone studies. There was no significant difference between the mean serum LH in the saline and naloxone groups, and the mean serum progesterone concentration was not significantly altered.(ABSTRACT TRUNCATED AT 250 WORDS)