Brain reward systems are thought to be involved in the reinforcing effect of both cocaine and opiates. In vitro receptor autoradiography was used to determine the effect of chronic, continuous cocaine exposure of 2 weeks duration on [3H]naloxone binding in various regions of rat brain. Although cocaine action in the central nervous system is usually associated with altered dopamine function, we observed that opiate receptor density as labeled by [3H]naloxone was altered by chronic cocaine exposure in critical brain reward regions, including the nucleus accumbens, ventral pallidum, and lateral hypothalamus. Endogenous opioid activity at opiate receptors in these critical regions may be associated with the reinforcement induced by both cocaine and opiates.