We report the case of an occasional intravenous drug user who developed two successive hepatitis C virus (HCV) infections. The first infection led to seroconversion (anti-HCV antibodies detected) and the detection of HCV RNA in serum. After a spontaneous recovery (normalization of alanine aminotransferase levels and HCV RNA clearance), a second HCV infection was observed, with the recurrence of HCV viremia. Antibody directed against HCV serotype 1 was detected throughout the follow-up monitoring, but two different HCV strains were identified during the two infectious episodes: genotype 1a for the first and genotype 3a for the second. This observation shows that primary HCV infection does not confer protective immunity against subsequent infection with viruses of other genotypes. This may hamper the development of a vaccine. Conflicting results were obtained in genotyping and serotyping assays, suggesting that the serotyping method cannot be used to identify the HCV type in patients, such as intravenous drug users, who are exposed to successive HCV infections.