In October 1987, the New York State Department of Health initiated a study to determine the prevalence of antibody to HIV in clients of a facility for runaway and homeless adolescents in New York City. A risk-assessment component was added in May 1988. As of December 1989, a total of 2,667 adolescents had been tested, and 142 (5.3 percent) were found to be HIV-seropositive (males 6.0 percent, females 4.2 percent). The seroprevalence rate increased from 1.3 percent for 15-year-olds to 8.6 percent for 20-year-olds. Hispanics had the highest seroprevalence rate (6.8 percent), followed by non-Hispanic Whites (6.0 percent) and non-Hispanic Blacks (4.6 percent). HIV seropositivity was associated with intravenous drug use, male homosexual/bisexual activity, prostitution, and history of another sexually transmitted disease. The alarmingly high prevalence of HIV infection in this selected population illustrates the immediate need for prevention programs for adolescents.