Behavioral sensitization caused by repeated and intermittent administration of psychostimulants, such as cocaine and D-amphetamine, is accompanied by enhanced function in limbic-motor circuitry that is involved in the generation of motivated behavior. The present microdialysis study investigated the effect of D-amphetamine-induced sensitization on dopamine (DA) efflux in the nucleus accumbens (NAC) of male rats during sexual behavior. Male rats were given one injection of D-amphetamine (1.5 mg/kg, i.p.) or saline every other day for a total of 10 injections. Three weeks after discontinuation of drug treatment, rats were tested for sexual behavior during a test in which microdialysis was performed. There was an augmented efflux of DA in the NAC of D-amphetamine-sensitized rats compared with nonsensitized control rats when a receptive female was present behind a screen (35 vs 17%). Sensitized rats exhibited facilitated sexual behavior when the screen was removed, as indicated by a significantly shorter latency to mount and an overall increase in the amount of copulatory behavior. Although there was a significant increase in NAC DA concentrations from baseline in both sensitized and nonsensitized rats during copulation, there was a greater increase in DA efflux in the NAC of sensitized rats during the first 10 min copulatory sample (60 vs 37%). These results demonstrate that behavioral sensitization caused by repeated psychostimulant administration can "cross-sensitize" to a natural behavior, such as sex, and that increased NAC DA release may contribute to the facilitation of appetitive and consummatory aspects of this behavior.