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OBJECTIVES. To determine the risk of heterosexual transmission of hepatitis C virus (HCV) and to identify other risk factors for HCV seropositivity in heterosexual couples. DESIGN. Retrospective cross-sectional study comparing HCV-seropositive and HCV-seronegative heterosexual men and women. SETTING. Couples recruited from the community and screened for participation in a study of the heterosexual transmission of human immunodeficiency virus. PARTICIPANTS. A total of 340 subjects, 170 men and 170 women in sexual partnerships, aged 18 through 61 years. MAIN OUTCOME MEASURE. Seropositivity for HCV antibodies. RESULTS. Overall, 31 (18%) of the 170 women and 56 (33%) of the 170 men were positive by a four-antigen HCV immunoblot. Injection drug use and hemophilia were strongly associated with HCV seropositivity. Sixty-four percent of injection drug users were positive (odds ratio [OR], 27.0; 95% confidence interval [CI], 13.4 to 56.1; P < .0001), as were all four hemophiliacs in the study. History of blood transfusion was significantly associated with HCV seropositivity (OR, 2.7; 95% CI, 1.1 to 7.0; P = .02). Positivity for HCV was not associated with measures of sexual behavior within couples or with numbers of other sexual partners, history of sexually transmitted diseases, or human immunodeficiency virus seropositivity. However, two of the 31 women without parenteral risk but with a long-term HCV-positive male partner were HCV seropositive compared with none of 81 women with an HCV-negative male partner (P = .07). CONCLUSIONS. These results provide little evidence of HCV sexual transmission but are consistent with infrequent sexual transmission. They corroborate the importance of injection drug use and transfusion of blood or blood products in transmitting HCV and underscore the importance of ascertaining parenteral exposures when examining sexual transmission of HCV