Context and Objective: Despite having increased knowledge of the adverse reproductive effects of smoking, it is unclear whether nicotine affects the pulsatile LH secretion in humans. We addressed this issue in male and female smokers and nonsmokers. Subjects and Methods: Twenty-nine male and 16 female nonsmokers and smokers were recruited as volunteers. In male smokers, nicotine effect was also studied before and after quitting smoking. In females, cyclic ovulatory function was assessed by measuring basal body temperature, and sampling studies were performed during the follicular phase. In the morning of the sampling day, an iv catheter was inserted into an anterobrachial vein, and blood samples (1.0-1.5 ml each) were taken at 10-min intervals for 480 min, during which, at 240 min, nicotine was administered via a transdermal patch ( Nicotinell transdermal therapeutic system) containing 17.5 mg nicotine. Plasma LH was measured by immunoradiometric assay kits. Results: Nicotine significantly lengthened the interpulse interval of pulsatile LH secretion in male nonsmokers but not in female nonsmokers. In male smokers, nicotine did not lengthen the interpulse interval, and in female smokers it was also ineffective. After quitting cigarette smoking in male smokers, the refractory to nicotine effect disappeared within 1 wk. Conclusions: We conclude that nicotine inhibits pulsatile LH secretion only in males, and the tolerance developed to the nicotine effect disappears within 1 wk of quitting cigarette smoking. However, we cannot deny the possibility that nicotine effect would have been detected in females if more subjects had been studied.