Functional neuroimaging studies show substantial individual variation in brain activation accompanying the experience of emotion, including sadness. Here we used functional magnetic resonance imaging (fMRI) in 104 pairs of 8-year-old twins (47 MZ, 57 DZ) to assess genetic-environmental contributions to individual differences in neural activation in two prefrontal cortex (PFC) areas previously shown to be involved in sadness. No genetic effects were found for any area, individual environmental factors entirely accounting for individual variation in brain activation related to sadness. Sadness being the prevailing mood in depression, these findings may be of relevance to the etiology of childhood depressive disorders. Hum Brain Mapp 2007. © 2007 Wiley-Liss, Inc.