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The Baltimore Memory Study is a cohort study of the multilevel determinants of cognitive decline in 50-70-year-old randomly selected residents of specific city neighborhoods. Prior studies have demonstrated that cognitive function differs by race/ethnicity, with lower scores in minorities than in whites, but the underlying basis for these differences is not understood. Studies have differed in the rigor with which they evaluated and controlled for such important confounding variables as socioeconomic status (SES), health-related behaviors, comorbid illnesses, and factors in the physical environment. The goal of this study was to describe differences in neurobehavioral test scores by race/ethnicity, before and after control for a four-dimensional measure of SES and health-related behaviors and health conditions, in a cross-sectional analysis of first visit data. Random samples of households in the study area were selected until enrollment goals were reached. Among the 2,351 persons on whom eligibility was determined, 60.8% were scheduled for an enrollment visit; of these, 1,140 (81.3%) were enrolled and tested. These study participants were 34.3% male and 65.7% female and were from 65 Baltimore, Maryland, neighborhoods. After adjustment for age, sex, and testing technician, there were large and statistically significant differences in neurobehavioral test scores by race/ethnicity, with African-American scores lower than those for whites, for both men and women. After adjustment for individual SES (educational status, household income, household assets, and occupational status), the average difference declined by 25.8%. After additional adjustment for SES, health-related behaviors and health conditions, and blood lead, the average difference declined another 10%, but large differences persisted; African Americans had test scores that averaged 0.43 standard deviation lower than those for whites across all neurobehavioral tests. These differences were present in all cognitive domains, including tests that would not be characterized as susceptible to differential item functioning by race/ethnicity, suggesting that the results are not due to race/ethnicity-associated measurement error.