We studied the role of estrogens on LH pulse modulation in men in two ways. Firstly, we compared LH pulse frequency and amplitude in 13 normal men before and after 6 weeks administration of the antiestrogen tamoxifen (10 mg twice daily). Secondly, we compared LH pulse frequency and amplitude between a group of 10 agonadal men not receiving sex steroid treatment and a group of 9 agonadal men (male to female transsexuals) continuously treated with 50 ng ethinyl estradiol/day. Tamoxifen administration to normal men resulted in a significant rise in the mean serum LH level from 5.7 ± 1.3 (± SD) to 10.1 ± 2.4 U/L, which was associated with significant increases in LH pulse frequency (from 4.2 ± 1.5 to 5.8 ± 1.7/7 h) and LH pulse amplitude (from 3.8 ± 0.9 to 4.6 ± 0.7 U/L). In the group of agonadal men the mean LH pulse frequency was 6.8 ± 1.5/7 h, while it was 5.9 ± 1.7/7 h in the estrogen-treated agonadal group (P = NS). The mean serum LH level and LH pulse amplitude were, however, significantly lower in the estrogen-treated agonadal men than in the agonadal men (14.7 ± 7.0 vs. 34.3 ± 8.6 and 4.1 ± 1.8 vs. 7.4 ± 1.8 U/L, respectively). We conclude that estrogens reduce basal LH levels and LH pulse amplitude. With regard to the modulation of LH pulse frequency our data provide contradictory results. While an antiestrogen increased LH pulse frequency in normal men, estrogen alone produced no change in LH pulse frequency in agonadal men. The study design in the agonadal men ignores the possible interaction of the two major testicular hormones (estradiol and testosterone) on gonadotropin secretion. Therefore, a possible explanation for this discrepancy in the effects of antiestrogen and estrogen could be an interaction between estrogens and androgens on gonadotropin secretion at the level of the LHRH pulse generator.