To evaluate the role of altered luteinizing hormone (LH) release in the mechanism of polycystic ovarian disease (PCOD) anovulation, we have co-administered a gonadotrophin-releasing hormone (GnRH) antagonist and pulsatile GnRH therapy to two clomiphene citrate-resistant PCOD patients. The aim was to correct their inappropriate gonadotrophin secretion. Nal-Glu was administered s.c. every 72 h to both subjects for 3 weeks. On day 7 after commencing the study, intravenous pulsatile GnRH therapy was initiated (10 micrograms/pulse) every 90 min for 15 days to both subjects. In one subject, Nal-Glu treatment was continued and the GnRH dose was increased to 20 micrograms/pulse for 10 additional days. Prior to Nal-Glu, mean serum LH levels were 10.4 +/- 1.6 and 9.3 +/- 1.3 mIU/ml (mean +/- SEM) and mean interpulse intervals were 67.1 and 60 min in patients 1 and 2, respectively. Mean serum FSH levels were 4.9 +/- 0.4 and 4.2 +/- 0.2 mIU/ml for patients 1 and 2, respectively. LH pulsatility was abolished following Nal-Glu, mean serum LH decreased to 1.1 +/- 0.1 and 1.3 +/- 0.5 mIU/ml and mean FSH to 1.8 +/- 0.1 and 2 +/- 0.1 mIU/ml in the two subjects. On the 4th day of the combined therapy, mean serum LH increased to 5.4 +/- 1.3 and 3.9 +/- 0.9 mIU/ml with a mean interpulse interval of 72 and 80 min, respectively. Mean FSH levels increased to 3 +/- 0.1 and 2.8 +/- 0.1 mIU/ml, respectively and to 5.5 +/- 0.2 mIU/ml after the GnRH dose was increased in patient 2.(ABSTRACT TRUNCATED AT 250 WORDS)