BACKGROUND: Blacks have higher hypertension rates than whites, but the reasons for these disparities are unknown. Differential vulnerability, through which stress alters vulnerability to the effects of environmental hazards, is an emergent notion in environmental health that may contribute to these disparities. OBJECTIVES: We examined whether blacks and whites exhibit different associations between blood lead (BPb) and blood pressure (BP) and whether depressive symptoms may play a role. METHODS: Using the National Health and Nutrition Examination Survey 2005-2008, we regressed BP on the three-way interaction among race/ethnicity, BPb, and depressive symptoms in blacks and whites >/= 20 years of age. RESULTS: Blacks but not whites showed a positive association between BPb and systolic blood pressure (SBP). The disparity in this association between blacks and whites appeared to be specific to the high depressive symptoms group. In the low depressive symptoms group, there was no significant black-white disparity (betainteraction = 0.9 mmHg; 95% CI: -0.9, 2.7). However, of those with high depressive symptoms, blacks and whites had 5.6 mmHg (95% CI: 2.0, 9.2) and 1.2 mmHg (95% CI: -0.5, 2.9) increases in SBP, respectively, in association with each doubling of BPb (betainteraction = 4.4 mmHg; 95% CI: 0.5, 8.3). The pattern of results was similar for diastolic blood pressure. CONCLUSIONS: Our results suggest that depressive symptoms may contribute to the black-white disparity in the association between BPb and BP. Depressive symptoms may result, in part, from psychosocial stress. Our results support the notion that stress increases vulnerability to the health effects of environmental hazards and suggest that stress-related vulnerability may be an important determinant of racial/ethnic health disparities.