We aim to assess the prevalence of HIV sexual risk behaviours and substance use among runaway and homeless adolescents in San Francisco, Denver and New York City. Survey data were examined from 775 runaway and homeless adolescents recruited from street settings and youth agencies during 1992/1993. Nearly all (98%) reported having engaged in sexual intercourse, of whom 49% first had intercourse by the age of 13. Condom use during all vaginal intercourse in the previous 3 months was reported by 42%. Among males, 23% indicated that they had exchanged sex for money, as did 14% of the females. Ninety-seven per cent had used alcohol or drugs and 21% had injected drugs. Overall, 75% reported having had sex while under the influence of alcohol or drugs. Systematic epidemiological studies of this population and the development of innovative interventions are essential to reduce the threat of HIV among runaway and homeless youth.