It was suggested recently that a fundamental property of drugs that are rewarding, and thus have a high potential for abuse, is that they preferentially increase the extracellular concentration of dopamine (DA) in mesolimbic structures. This hypothesis was tested here by use of microdialysis in freely moving rats to determine the effects of systemic d-amphetamine administration on the extracellular concentration of DA in the so-called "limbic" (nucleus accumbens) and "motor" (dorsolateral caudate nucleus) subdivisions of the striatal complex. Amphetamine (2.03, 4.07, or 8.14 mumols/kg) greatly increased the extracellular concentration of DA in both structures, but there was no evidence of a preferential effect in the nucleus accumbens. The two higher doses of amphetamine actually increased extracellular DA to a greater extent in the dorsolateral caudate, but there was no significant regional difference if the data were expressed as a percent of baseline. These data do not support the hypothesis that drugs of abuse preferentially increase the extracellular concentration of DA in mesolimbic structures, although other ways in which amphetamine may selectively influence mesolimbic DA activity are discussed.