Most studies of human molecular genetics and social environment interactions on health have relied heavily on the classic diathesis-stress model that treats genetic variations and environments as being either "risky" or "protective." The biological susceptibility model posits that some individuals have greater genetic reactivity to stress, leading to worse outcomes in poor environments, but better outcomes in rich environments. Using a nontruncated measure of a chronic environmental stressor—socioeconomic status—measured by education, and two polymorphisms (5-HTTLPR and STin2 VNTR) of the serotonin transporter gene (5-HTT), we find strong evidence that some women are genetically more reactive to the environment, resulting in a crossover of risks of postpartum depression for the most reactive groups. We discuss how our approach and findings provide a framework for understanding some of the confusion in the gene-environment interaction literature on stress, 5-HTT, and depression.