Findings regarding the association between n-3 polyunsaturated fatty acid (PUFA) status and depression are conflicting. Thus, the authors studied associations between PUFA intake and depressive symptoms. In 1996, depressive symptoms were assessed in a subsample of participants from the Supplementation with Antioxidant Vitamins and Minerals (SU.VI.MAX) Study using the Center for Epidemiologic Studies Depression Scale (CES-D). In 2007-2009, information on CES-D score, history of depression, and use of antidepressant medication was obtained. Intakes of n-3 PUFAs were estimated from repeated 24-hour dietary records collected during 1994-1996. Subjects with depressive symptoms (cases) were identified using CES-D scores greater than 15 and/or antidepressant use. Logistic regression analyses were used. Cross-sectional (n = 2,744) and longitudinal (n = 1,235) associations between quartiles of PUFA intake and depressive symptoms were estimated. In cross-sectional analyses, quartile of n-3 PUFA intake was associated with lower odds of depressive symptoms (fourth quartile vs. first: odds ratio = 0.74, 95% confidence interval: 0.58, 0.95; P for trend = 0.001). No association between PUFA intake and incidence of depressive symptoms over 13 years was detected. This study provides new insights into the PUFA-depression link. While no association between n-3 PUFA intake and incidence of depressive symptoms was detected, an association was observed in cross-sectional analyses, which may reflect unhealthy dietary patterns among subjects with depressive symptoms.