This study was performed to identify specific high-risk behaviors, such as unprotected oral, anal, and vaginal intercourse and substance abuse, associated with human immunodeficiency virus infection among adolescents attending three diverse clinics located in a localized geographic area: a university-based clinic, a Planned Parenthood clinic, and an inner-city public health clinic (PHC). Six hundred seventy-one female and 207 male adolescents attending one of the three clinics completed a structured questionnaire. Similarities among patients at the clinic sites included high rates of anal intercourse (21%), unprotected vaginal sex (95%), oral sex (73%), and poor communication skills (42%). Some differences appeared as well, including higher rates of homosexual experiences, no birth control use, and having multiple partners among adolescents attending the PHC (p < 0.001). In contrast, adolescents attending either the university-based clinic or the Planned Parenthood Clinic had higher rates of substance abuse around sexual activity than those who attended the PHC (p < 0.001). We conclude that adolescents attending general medical clinics in the San Francisco Bay area engage in high-risk behaviors that place them at risk for transmission of human immunodeficiency virus even though many have had previous education about acquired immunodeficiency syndrome and sexually transmitted disease. Specific risk factors include unprotected receptive anal intercourse, unprotected vaginal intercourse with new and unknown partners, experience in homosexual behavior, high rates of oral sex, multiple partners, poor communication skills, and frequent use of illicit substances in conjunction with sex. The differences found among sites indicate the need for health care providers and prevention programs to provide emphasis on practices specific to the adolescents in their service area.