Data were collected from students attending high school in a rural, low acquired immunodeficiency syndrome (AIDS) prevalence community in Northern California, and compared with students in an inner-city AIDS epicenter (San Francisco). The findings demonstrate that rural adolescents have higher levels of human immunodeficiency virus (HIV) knowledge, especially about risk-reduction strategies. However, rural adolescents also report higher rates of HIV-related sexual risk behaviors. Rural adolescents may not perceive the personal salience of practicing HIV risk-reduction behaviors thus increasing their risk for exposure to sexually-transmitted diseases, including HIV infection. School-based HIV prevention programs developed for rural communities will need to enhance the personal salience of HIV for adolescents' and discourage their discounting of personal risk attributable to a lower prevalence of AIDS in the community. Physicians must become more actively involved in HIV prevention efforts by routinely assessing adolescent patient's sexual behavior and utilizing their clinical interaction to provide HIV education and promote the adoption of HIV risk-reduction behaviors.