5-HTTLPR, episodic stressors, depressive and anxious symptoms were assessed prospectively (child and parent report) every 3 months over 1 year (5 waves of data) among community youth ages 9 to 15 (n = 220). Lagged hierarchical linear modeling analyses showed 5-HTTLPR interacted with idiographic stressors (increases relative to the child's own average level over time), but not nomothetic stressors (higher stress exposure relative to the sample), to predict prospective elevations in depressive, but not anxious, symptoms. Youth with copies of the S or L(G) alleles of 5-HTTLPR, who experienced more stressors relative to their typical level, exhibited prospective increases in depressive symptoms over time. These findings suggest that 5-HTTLPR confers susceptibility to depression via stress reactivity.