We reviewed 92 published and unpublished studies of the prevalence of infection with the human immunodeficiency virus (HIV) among intravenous drug users (IVDUs) in the United States. Human immunodeficiency virus seroprevalence among IVDUs in drug treatment programs in the United States ranged from 0% to 65%. Seroprevalence was highest in the Northeast (10% to 65%) and Puerto Rico (45%to 59%); lower in the South Atlantic (7% to 29%) and in the metropolitan areas of Atlanta, Ga (10%), Detroit, Mich (7% to 13%), and San Francisco, Calif (7% to 13%); and 5% or less in other areas of the West, the Midwest, and the South. Among IVDUs seen in drug treatment programs, risk of infection was not associated with gender or age but was associated with black and Hispanic ethnicity, male homosexual orientation, and certain intravenous drug—use practices. Cross-sectional and cohort studies indicated increases in seroprevalence of between 0% and 14% per year among IVDUs in treatment. We estimated that between 61 000 and 398 000 IVDUs in the United States were infected with human immunodeficiency virus, or 5% to 33% of the IVDU population. High rates of infection among IVDUs in treatment in the Northeast indicate the potential for rapid spread in regions where rates are currently low. An urgent need exists to monitor human immunodeficiency virus infection levels and trends more widely and to develop effective programs to reduce the further spread of human immunodeficiency virus infection among IVDUs.