The present study was designed to evaluate the effect of different serum concentrations of estradiol-17 beta (E2) on pituitary luteinizing hormone (LH) release in postmenopausal women. Serum E2 levels were evaluated in healthy postmenopausal women while they wore two, four, and six transdermal E2 delivery systems. The mean serum E2 levels at 48 hours after application of the devices were 185.5, 338.9, and 520.5 pg/mL, respectively, which were significantly different from each other. Serum E2 levels were stable throughout the first 48 hours of patch application but declined by a mean of 54% between 48 and 72 hours. Pituitary LH surges were induced with all three serum concentrations of E2 but were present more often with the higher serum values. There were no significant differences between the mean interval of device utilization and initiation, height, or duration of the induced pituitary LH surge at any of the three serum E2 concentrations studied.