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Background: Literature pertaining to the relationship between workplace factors and depression has been compartmentalized: work conditions, family conditions, and work–family balance have been studied separately as predictors of depressive symptoms but not concurrently. Objective: Work conditions and work–family spillover were considered concurrently as modifiable workplace factors associated with depressive symptomatology, while controlling for confounding socio-economic factors. Methods: This cross-sectional study involved 218 female health care workers who completed a survey assessing work conditions [Effort–Reward Imbalance (ERI) scale and Job Content Questionnaire (JCQ)], work–family balance (work–family spillover scale), sociodemographic information, and depressive symptoms [Center for Epidemiological Studies Depression (CES-D) scale]. Results: Path analysis supported the presence of a direct relationship between depressive symptoms and high effort–reward imbalance, high negative work–family spillover, low positive family-to-work spillover, and low education. The indirect effect of low support from work was mediated by negative work-to-family spillover and high effort–reward imbalance. The indirect effect of high effort–reward imbalance was mediated by increased negative work-to-family spillover. The indirect effect of having children 18 years or younger was mediated by decreased positive family-to-work spillover. An indirect effect of low education was mediated by high effort–reward imbalance and high negative work-to-family spillover. Conclusions: The association between work conditions and depressive symptomatology is mediated by increased negative work-to-family spillover. The impact of having young children is mediated by decreased positive family-to-work spillover. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]