Sexual experience, like repeated drug use, produces long-term changes including sensitization in the nucleus accumbens and dorsal striatum. To better understand the molecular mechanisms underlying the neuroadaptations following sexual experience, we employed a DNA microarray approach to identify genes differentially expressed between sexually experienced and sexually naive female hamsters within the nucleus accumbens and dorsal striatum. For 6 weeks, a stimulus male was placed in the home cage of one-half of the hormonally primed, ovariectomized female hamsters. On the seventh week, the two experimental groups were subdivided, with one half paired with a stimulus male. In comparison with sexually naive animals, sexually experienced hamsters receiving a stimulus male on week 7 exhibited an increase in a large number of genes. Conversely, sexually experienced female hamsters not receiving a stimulus male on week 7 exhibited a reduction in the expression of many genes. For directional changes and the categories of genes regulated by the experimental conditions, data were consistent across the nucleus accumbens and dorsal striatum. However, the specific genes exhibiting changes in expression were disparate. These experiments, among the first to profile genes regulated by female sexual behavior, will provide insight into the mechanisms by which both motivated behaviors and drugs of abuse induce long-term changes in the mesolimbic and nigrostriatal dopamine pathways.