OBJECTIVE: The study examined gender differences in extrastriatal dopamine D2-like receptor levels in the human brain in vivo. METHOD: [11C]FLB 457, a high-affinity radioligand for extrastriatal D2-like receptors, and a three-dimensional positron emission tomography system were used to measure D2-like receptor binding potentials in frontal cortex, temporal cortex, and thalamus in 12 healthy men and 12 healthy women. RESULTS: Women had higher D2-like receptor binding potentials than men in the three brain regions studied, and the difference in the frontal cortex was statistically significant. In a more detailed regional analysis, the difference between the sexes was most pronounced for the left and right anterior cingulate cortex. CONCLUSIONS: This study provides in vivo evidence for a gender difference in dopamine D2-like receptor levels, which could be reflected in gender-associated differences in clinical disorders linked to the dopamine system.