Gender differences have been observed in a number of aspects of the pharmacology of opiates, including their antinociceptive activity, discriminative stimulus properties, the generation of physical dependence, and their positive reinforcing properties. The current experiments were carried out to rigorously examine whether gender differences exist in the intravenous (IV) self-administration of opiates in an operant conditioning paradigm. Both dose-response analyses and the determination of the strength of the reinforcing properties of opiates using a "breakpoint" analysis were examined. We found strong gender differences in the IV self-administration of two mu opiate agonists-heroin and morphine. At a standard fixed ratio (FR) of responding, females consumed significantly greater amounts of heroin and morphine than did males in a dose-dependent fashion. In addition, females also showed much higher breakpoints than did males: the highest FR breakpoint achieved in females was more than double that observed in males and the frequency distribution of breakpoints was shifted significantly to the right in females when compared to males. These data collectively show that mu opiate agonists may serve as reinforcing agents in females over a broader dose range than males and that they also self-administer considerably more opiates on a milligram per kilogram basis. Finally, we conclude that they will also expend much greater effort in an operant conditioning task to obtain opiate reinforcement.