Blood pressure varies during the menstrual cycle, but the reason for this is unclear. Administration of (synthetic) sex hormones can influence the level of vasoactive substances such as endothelin (ET). However, it is not known whether short-term variations in sex hormone levels in physiological situations affect ET levels. We assessed the effects of the menstrual cycle on plasma ET-1 in 8 healthy premenopausal women not using oral contraceptives (OCs) and 8 premenopausal women using OCs. ET-1 levels were measured in all subjects on days 1 to 3 (menstrual phase), 9 to 12 (follicular phase), and 20 to 23 (luteal phase) of the menstrual cycle. ET-1 levels remained constant in OC users (2.4 +/- 0.4, 2.6 +/- 0.4, and 2.4 +/- 0.4 pg/mL on days 1 to 3, 9 to 12, and 20 to 23 of the pill cycle). In contrast, ET-1 levels in non-OC users decreased in all women during the follicular and luteal phase of the menstrual cycle compared with the menstrual (low-estrogenic) phase (3.6 +/- 0.5, 2.8 +/- 0.5, and 2.9 +/- 0.3 pg/mL for the menstrual, follicular, and luteal phase, respectively, P < .01 for menstrual vfollicular and P < .01 for menstrual v luteal). The differences between OC users and nonusers were significant in the menstrual phase of the cycle (P < .01). We conclude that ET levels fluctuate during the menstrual cycle. Previously reported effects of the menstrual cycle on blood pressure may be partly explained by the effects of sex hormones on the level of vasoactive mediators. This fluctuation is not present in OC users. Studies on hemodynamic parameters in premenopausal women should account for hormonal variations in the various phases of the menstrual cycle.