Young persons who engage in unprotected sexual intercourse or use injection drugs are at increased risk for human immunodeficiency virus (HIV) infection. To examine changes in HIV-related risk behavior among high school students in the United States during 1991--2005, CDC analyzed data from eight national Youth Risk Behavior Surveys (YRBS) conducted during that period. This report summarizes the results of that analysis, which indicated that, during 1991--2005, the percentage of U.S. high school students engaging in HIV-related sexual risk behaviors decreased. During 1995--2005, the percentage of U.S. high school students who ever injected drugs remained less than 4%. However, many students still engage in HIV-related risk behaviors. Measures aimed at changing these behaviors should be strengthened to decrease the incidence and prevalence of HIV/AIDS among young persons and meet the national 2010 objective for adolescent sexual behavior.