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Path analysis was used to investigate factors associated with self-reported sexually transmitted diseases among 569 homeless and runaway adolescents in four Midwestern states. Youth were interviewed by outreach workers directly on the streets, in shelters, and in drop-in centers. Results indicated that family abuse was positively related to substance use, affiliation with friends who sold sex, and time on own. Early family abuse indirectly increased the likelihood of self-reported sexually transmitted diseases through time on own, substance use, friends selling sex, and risky sexual behaviors. Finally, substance use and affiliation with friends who sold sex was positively associated with risky sexual behaviors, which in turn was related to self-reported sexually transmitted diseases. No significant gender interactions were found for this model.