The hypothesis that separate neural systems mediate the reinforcing properties of opiate and psychomotor stimulant drugs was tested in rats trained to lever-press of IV injections of either cocaine or heroin during daily 3-h sessions. Pretreatment with the opiate receptor antagonist drug naltrexone produced dose-dependent increases in heroin self-administration, but had no effect on the rate or pattern of cocaine self-administration. Similarly, pretreatment with low doses of the dopamine antagonist drug alpha-flupenthixol produced dose-dependent increases in cocaine but not heroin self-administration. High doses of alpha-flupenthixol eliminated all responding for cocaine and slightly reduced heroin self-administration. The specificity with which the two antagonist drugs exerted their behavioral effects strongly suggests that independent neural substrates are responsible for the reinforcing actions of heroin and cocaine.