Previous research suggests that the female sex hormones may moderate cardiovascular and mood responses to cigarette smoking and abstinence. To test this possibility, acute effects of cigarette smoking on cardiovascular reactivity and mood were examined in 12 oral contraceptive users and 12 nonusers across two menstrual phases (early and late cycle). After overnight deprivation, each participant attended two sessions in which they first sham-smoked and then smoked two standard cigarettes, via a quantified smoke delivery system. Oral contraceptive users exhibited larger cigarette smoking-induced increases in heart rate compared with nonusers. In addition, cigarette smoking-induced cardiovascular changes varied with both the phase of the menstrual cycle and oral contraceptive use. No menstrual phase-dependent effects were observed for tobacco withdrawal symptoms, premenstrual symptoms, or moods prior to smoking. Cardiovascular hyperreactivity to cigarette smoke in oral contraceptive users may help explain the mechanisms by which smoking and oral contraceptive use contribute to an elevated risk for coronary heart disease.