Background: Recent investigations suggest a common genetic rather than environmental cause to explain the association between IgE-mediated atopic allergies and depression. Objective: Taking into account psychosocial confounding factors, we investigated separately and at the epidemiologic level the effects of maternal, paternal, and sibling atopy on the cumulative incidence of a child's depression. Methods: We used an unselected, genetically homogenous, general population birth cohort of 12,058 live-born children in Finland. The 31-year prospective follow-up included questionnaire information on atopic disorders of the cohort members' parents and siblings. The probands' own atopic conditions were evaluated by means of skin prick tests, and information on lifetime depression diagnoses was gleaned from postal questionnaires and national hospital discharge registers. Potential confounders were mother's parity, father's social class, maternal smoking during pregnancy, proband's regular daily smoking, and proband's dwelling place. Total variable information was available from 4068 cohort members. Results: Among female probands, the presence of atopy in parents was the strongest predictor for lifetime depression (P < .001), and sibling atopy and parental atopy were the strongest predictors for hospital-treated depression (P = .018 and P = .036, respectively). After controlling for confounders, it was noticed that maternal atopy increased a female proband's risk of lifetime depression up to 1.9-fold (odds ratio, 1.9; 95% CI, 1.1-3.0). The corresponding risk increased over 4-fold if parental-maternal atopy was combined with proband's own atopy. Conclusions: Our findings suggest that maternal inheritance could be a significant causative factor in the association between atopy and depression of female probands. (J Allergy Clin Immunol 2003;111:1249-54.)