Background and Objectives: The major routes of transmission for hepatitis C virus (HCV) appear to be blood transfusion and injecting drug use (IDU). There is still some controversy concerning the role of sexual transmission in HCV infection., Goal of This Study: To use a well characterized, high-risk population of STD clinic patients to investigate the role of sexual transmission of HCV and to determine any association between HCV, HBV, and HIV., Study Design: We tested stored sera obtained anonymously from clients attending three STD clinics in North Carolina in 1988 for antibodies to HCV and hepatitis B virus (HBV). An anonymous, self-administered client questionnaire provided patient history and demographic information., Results: The most important risk factor for either HCV or HBV seropositivity was IDU. The only risk factor associated with HCV seropositivity after the removal of IDUs was age older than 30 years. In contrast, risk factors associated with HBV seropositivity after the removal of IDUs included male gender, age older than 30 years, HIV seropositivity, homosexuality/bisexuality, syphilis seropositivity, and a history of syphilis., Conclusion: Our study of STD clients confirms the important role that IDU plays in infection with HCV, but suggests that sexual transmission plays only a minor role in HCV epidemiology.