A growing number of recent reports have demonstrated sex and menstrual cycle differences in the subjective, physiological and pharmacokinetic effects of stimulant drugs in humans. The present study was conducted to further investigate the relationship between gonadal hormones and cocaine effects by examining whether oral contraceptives (OCs) alter the acute effects of cocaine. Seven female volunteers, who were taking triphasic OCs and who were occasional users of cocaine, provided informed consent and participated in this placebo-controlled, four-visit study. Subjects were studied twice during days 6-10 of the menstrual cycle (equivalent to the follicular phase) and twice during days 21-28 of the menstrual cycle (equivalent to the luteal phase) and were challenged with an acute dose of intranasal (in) cocaine (0.9 mg/kg or placebo). There were no differences in cocaine-induced subjective, physiologic or plasma cocaine and metabolite levels during the times equivalent to the follicular and luteal phases of the menstrual cycle. Our findings provide evidence that OCs do not present an added risk of cocaine-induced cardiovascular effects and that exogenous administration of estrogen and progesterone at the physiologic doses found in OCs do not alter the subjective responses to acute cocaine.