This cross-sectional study of 341 entrants to drug abuse treatment in four Connecticut cities in 1986-1987 evaluated whether demographic, behavioral, viral serologic, or economic differences explained the disproportionate risk of human immunodeficiency virus type 1 (HIV-1) infection among black and Hispanic intravenous drug users (IVDUs), relative to non-Hispanic white IVDUs. Blacks [odds ratio (OR) = 9.0, 95% confidence interval (CI) = 5.1-15.9] and Hispanics (OR = 4.1, 95% CI = 1.9-8.8) were at increased risk of HIV-1 infection, relative to non-Hispanic whites. Those who lived closer to New York City, injected drugs more frequently, used intravenous drugs for a longer duration, used shooting galleries, had greater numbers of sexual partners, had human cytomegalovirus (CMV) or hepatitis B virus (HBV) antibodies, and had the lowest annual incomes were also at increased risk. However, none of these other factors accounted for the black and Hispanic HIV-1 risk in stratified analysis. Black race, Hispanic ethnicity, proximity to New York City, and number of drug injections in the past year each also remained significant, independent risk factors in a multivariate analysis. The increased HIV-1 risk of nonwhite IVDUs remained unexplained. Behavioral, sociologic, and/or biologic factors not identified in this study may modulate HIV-1 transmission dynamics in IVDUs.