To identify risk factors for human immunodeficiency virus (HIV) infection in intravenous drug users, we undertook a study of the seroprevalence of HIV antibody in 452 persons enrolled in a methadone-treatment program in the Bronx, New York. The seroprevalence of HIV was 39.4 percent overall, 49.1 percent in blacks, 41.8 percent in Hispanics, and 17.2 percent in non-Hispanic whites (P less than 0.001 for all comparisons). The presence of HIV antibody was associated with the number of injections per month (P less than 0.001), the percentage of injections with used needles (P less than 0.001), the average number of injections with cocaine per month (P less than 0.001), and the percentage of injections with needles that were shared with strangers or acquaintances (P less than 0.001), a practice that was more common among blacks and Hispanics than among whites. The number of heterosexual sex partners who used intravenous drugs was associated with HIV infection in women (P less than 0.004) and was the only risk factor found for users who had not injected drugs after 1982 (P less than 0.05). The presence of HIV antibody was independently associated with being black or Hispanic (adjusted odds ratio, 4.56; 95 percent confidence interval, 2.65 to 8.14), a more recent year of the last injection of drugs (adjusted odds ratio, 1.24; 95 percent confidence interval, 1.13 to 1.35), the percentage of injections of drugs that took place in "shooting galleries" (adjusted odds ratio, 1.49; 95 percent confidence interval, 1.19 to 1.88), having sex partners who used intravenous drugs (adjusted odds ratio 1.24; 95 percent confidence interval, 1.06 to 1.45), and low income (adjusted odds ratio, 1.55; 95 percent confidence interval, 1.10 to 2.17). We conclude that differences in both the social setting of drug use and behavior related to injection carry different risks for infection with HIV and may explain, in part, the higher seroprevalence of HIV among blacks and Hispanics. In addition, we found that heterosexual activity was an independent risk factor for drug users.