Studies have found abnormalities of resting EEG measures of hemispheric activity in depressive disorders. Similar EEG findings and a prominent thinning of the cortical mantle have been reported for persons at risk for depression. The correspondence between EEG alpha power and magnetic resonance imaging (MRI) measures of cortical thickness was examined in a multigenerational study of individuals at risk for depression. Seventy-five participants underwent resting EEG and approximately 5 years later underwent MRI scanning. High-risk participants (n = 37) were biological descendants of probands having major depression and low-risk participants (n = 38) were descendants of individuals without a history of depression. EEG alpha power was interpolated across the surface of a template brain and coregistered with measures of cortical thickness. Voxel-wise correlations of cortical thickness and alpha power were computed while covarying for age and gender. The high-risk group, when compared to the low-risk group, showed greater alpha asymmetry in an eyes-closed condition, with relatively less activity over right parietal cortex. Alpha power correlated inversely with cortical thickness, particularly over the right posterior region, indicating that EEG evidence of reduced cortical activity was associated with increased cortical thinning. This is the first report of widespread correlation of EEG alpha activity with MRI measures of cortical thickness. Although both EEG and MRI measures are associated with risk for depression, we did not detect evidence that cortical thickness mediated the alpha asymmetry findings. Thus, alpha asymmetry, alone or in combination with MRI, may be a marker of vulnerability for a familial form of depression. Hum Brain Mapp, 2011. © 2011 Wiley Periodicals, Inc.