Hepatitis C is a significant public health issue in the Languedoc-Roussillon region. Little epidemiological data is available, particularly regarding genotypes 4, 5, and 6. Our objective was to describe cases of HCV infection (genotypes 4, 5, and 6) diagnosed between 1993 and 2008 in patients residing in the Languedoc-Roussillon region, within a network of laboratories. A total of 443 cases were included, of which 376 were genotype 4 (including 187 subtypes 4a and 156 subtypes 4d), 63 were genotype 5, and 4 were genotype 6. The annual number of diagnosed cases had been declining since 1999. Genotype 4 was associated with male sex, younger age, intravenous drug use, and co-infection with HBV or HIV. This association was particularly strong for subtype 4d. These data highlight the need to target hepatitis C control programs and to strengthen efforts to reduce the risk of HCV transmission among drug users. (R.A.)