Prior work in cultural psychology and cultural neuroscience shows that culture (defined as a loosely organized set of practices and meanings) has systematic influences on psychological processes that are reflected in judgment, memory, and decision-making, as well as in functional brain activations that are linked to these domains (1, 2). However, it is not as yet clear whether the cultural influences might extend to structural properties of the brain such as the volume of different cortical and subcortical regions. Nor is it clear whether the cultural difference in the regionally specific brain volume could be attributed to cultural experience. To explore these questions, we have investigated whether the cultural dimension of independent versus interdependent self-construal would be related to brain volume. In support of the hypothesis that interdependence is linked to the down-regulation of a strategic pursuit of self-interest, we have found that the volume of the bilateral orbitofrontal cortex inversely predicts interdependent self-construal (3). Further, we have underscored the critical role of experience in the OFC volume difference by utilizing a genetic means. Specifically, while the OFC volume tends to be less in interdependent vs. independent cultures, this cultural difference is apparent only among those carrying genetic polymorphisms that are known to support environmental influences. Implications for future research on culture, genes, and the brain will be discussed.