In recent years, epidemiologists have established major variations in the incidence of schizophrenia and have begun to investigate the causes of these variations. The report by Pedersen and Mortensen (Am J Epidemiol 2006;163:971-8) in this issue of the Journal examines the contribution of family-level factors to the urban-rural difference in the incidence of schizophrenia. Their results suggest that familial life in urban environments confers some effect that persists after families move to rural settings. Taking these findings together with those of previous studies, it appears that factors operating at the level of the social context, the family, and the individual may all contribute to the urban-rural difference in schizophrenia incidence. This work exemplifies an integrative, multilevel approach to epidemiologic research that employs principles central to eco-epidemiology and other, similar frameworks.