Before the 1970s, today's older Americans were exposed to high levels of lead in the environment. The authors previously reported that lifetime cumulative lead dose was associated with lower cognitive test performance in older adults. Experiments suggest that environmental stress may intensify the detrimental influence of lead. No large, population-based studies of this question have been done. The authors evaluated whether cross-sectional associations of tibia lead with cognitive function were modified by neighborhood psychosocial hazards in the Baltimore Memory Study (2001-2005), a longitudinal cohort study of determinants of cognitive decline. Tibia lead was measured via (109)Cd-induced K-shell X-ray fluorescence. Neighborhood psychosocial hazards were measured independently of study subjects. Complete data were available among 1,001 demographically diverse adults aged 50-70 years, randomly selected from 65 contiguous neighborhoods in Baltimore City. Hierarchical mixed-effects regression models showed that neighborhood psychosocial hazards exacerbated the adverse associations of tibia lead in 3 of 7 cognitive domains after adjustment for age, sex, race/ethnicity, education, testing technician, and time of day (language, P = 0.039; processing speed, P = 0.067; executive functioning, P = 0.025). The joint occurrence of environmental stress and lead exposure across the life span may partially explain persistent racial/ethnic and socioeconomic disparities in cognitive function in late life.