The transmission of the hepatitis C virus (HCV) remains high among people who inject drugs (PWID). While harm reduction policies that promote IDUs’ access to sterile syringes and substitution treatments have significantly reduced the transmission of the human immunodeficiency virus (HIV), their impact on HCV transmission is currently limited or nonexistent. This difference stems from the fact that the prevalence of HCV infection is much higher than that of HIV, and that the risk of HCV transmission through blood is higher than that of HIV when sharing injection preparation equipment. To determine the incidence of HCV infection among IDUs in northeastern France as well as residual modes of transmission, a prospective cohort study of HCV-seronegative IDUs was conducted between 1999 and 2001. (R.A.)