This study explored whether adolescents with elevated symptoms of mania (ESM+) engage in more HIV risk behaviors than those with other psychiatric disorders and examined factors associated with HIV risk behavior among ESM+ adolescents. Eight hundred forty adolescents (56% female, 58% African American, "M" age = 14.9 years) who received mental health treatment completed private, computer-based assessments of psychiatric disorders and of sexual and substance use behaviors and provided urine to screen for sexually transmitted infections (STI). Eighty-seven percent met criteria for a psychiatric disorder, and among these youth 21% were considered ESM+. Compared to those with other psychiatric disorders, ESM+ were more likely to be sexually active (61.6% vs. 53.6%), have multiple sexual partners (58.6% vs. 37.5%), have unprotected sex (38.4% vs. 28.0%), exchange sex for money (4.7% vs. 1.2%), and test positive for an STI (14.0% vs. 6.3%). Among ESM+ youth, sexual risk behaviors were primarily associated with individual factors (e.g., self-efficacy, impulsivity, and substance use) and varied depending on the type of sexual behavior (e.g., onset of sex, number of partners, and condom use). Adolescents with ESM should be regularly screened for sexual risk behaviors and receive HIV prevention skills. Efforts to increase self-efficacy for safer sex, reduce impulsivity, and decrease substance use may be effective targets for sexual risk reduction among adolescents with ESM. (Contains 3 tables and 1 figure.)