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Background: Although depressive symptoms during pregnancy have been related to negative maternal and child health outcomes such as preterm birth, low birth weight infants, postpartum depression, and maladaptive mother-infant interactions, studies on the impact of neighborhood environment on depressive symptoms in pregnant women are limited. Pregnant women residing in disadvantaged neighborhoods reported higher levels of depressive symptoms and lower levels of social support. No researchers have examined the relationship between neighborhood environment and avoidance coping in pregnant women. Guided by the Ecological model and Lazarus and Folkman's transactional model of stress and coping, we examined whether social support and avoidance coping mediated associations between the neighborhood environment and depressive symptoms in pregnant African-American women., Methods: Pregnant African-American women (n = 95) from a medical center in Chicago completed the instruments twice during pregnancy between 15 and 25 weeks and between 25 and 37 weeks. The self-administered instruments measured perceived neighborhood environment, social support, avoidance coping, and depressive symptoms using items from existing scales. Objective measures of the neighborhood environment were derived using geographic information systems., Findings: Perceived neighborhood environment, social support, avoidance coping, and depressive symptoms were correlated significantly in the expected directions. Objective physical disorder and crime were negatively related to social support. Social support at time 1 (20 ± 2.6 weeks) mediated associations between the perceived neighborhood environment at time 1 and depressive symptoms at time 2 (29 ± 2.7 weeks). An increase in avoidance coping between times 1 and 2 also mediated the effects of perceived neighborhood environment at time 1 on depressive symptoms at time 2., Conclusion: Pregnant African-American women's negative perceptions of their neighborhoods in the second trimester were related to higher levels of depressive symptoms in the third trimester. If these results are replicable in prospective studies with larger sample sizes, intervention strategies could be implemented at the individual level to support pregnant women in their ability to cope with adverse neighborhood conditions and ultimately improve their mental health., (Copyright © 2015 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.)