In this article, we present data obtained with the psychosocial interview instrument, HEADSS (Home, Education, Activities, Drug use and abuse, Sexual behavior, Suicidality and depression) that was administered to High Risk Youth Clinic clients at their initial visits during a 1-year period. Of the 1,015 new patients, 63% were homeless/runaway youths and 37% were living with their families. Utilizing the HEADSS interview instrument, we compared homeless/runaway youths to nonhomeless youths in a number of areas, including risks for human immunodeficiency virus (HIV) infection. Our results showed that homeless teens tended to be younger, female, and white compared to their nonhomeless counterparts. They were more likely to have dropped out of school and were far more likely to be depressed and actively suicidal. They demonstrated all forms of drug abuse. They engaged in first sexual intercourse at an earlier age, and experienced a higher incidence of sexual abuse and prostitution. They were 6 times more likely to be at risk for HIV infection.