Clinical studies suggest that cocaine disrupts reproductive function, but because cocaine abusers often abuse opiates and alcohol, it has been difficult to determine the contribution of cocaine alone. The effects of chronic cocaine self-administration on menstrual cycle duration and basal levels of progesterone were examined in eight female rhesus monkeys and compared with the effects of occasional administration of single cocaine doses (0.4 or 0.8 mg/kg) in six otherwise drug-free controls. All monkeys had normal ovulatory menstrual cycles before cocaine exposure. Monkeys self-administered cocaine (0.10 mg/kg/injection) and food (1 gm banana pellets) in 4 daily sessions on a second-order schedule (fixed ratio 2 [variable ratio 16:S]). Cocaine intake was limited to 8 mg/kg/day. During the first cocaine exposure (256-776 days), monkeys self-administered 3.51 (+/- 0.77) to 7.41 (+/- 0.27) mg/kg/day. During the second cocaine exposure (103-623 days), monkeys self-administered 6.18 (+/- 0.77) to 7.41 (+/- 0.27) mg/kg/day. In these prospective longitudinal studies, 48% of the menstrual cycles were of abnormal duration in the cocaine self-administration group, whereas only 6% of the menstrual cycles were abnormal in the control group. There were 19 episodes of amenorrhea (61-190 days of no menses). During cocaine self-administration, approximately one-third of the menstrual cycles were anovulatory with low mid-luteal progesterone levels of 2.04 (+/- 0.6) to 4.13 (+/- 0.5) ng/ml. Over 25% of menstrual cycles were anovulatory during cocaine withdrawal with mid-luteal progesterone levels below 5 ng/ml. These data indicate that chronic cocaine exposure can disrupt the menstrual cycle in rhesus monkeys and that menstrual cycle abnormalities often persist during cocaine withdrawal. These data are consistent with clinical studies and reports of cocaine-induced disruption of the estrous cycle in rodents.