The prevalence, risk factors, and incidence of hepatitis C virus (HCV) infection were studied in a cohort of drug users in Amsterdam. In intravenous drug users, the seroprevalence was 74% (224/304) versus 10% (4/42) in nonintravenous drug users. Risk factors independently associated with HCV antibody seropositivity were history and duration of intravenous drug use and frequency of injections. Daily smoking of heroin in the previous 6 months was independently associated with the absence of HCV antibodies. Periods of fever, tiredness, and diarrhea in the preceding 6 months were associated with HCV antibodies even after correction for human immunodeficiency virus infection. The incidence rate of HCV infection appeared high and stable over the years 1986 to 1989. Thus, HCV infections are common among intravenous drug users and are mainly due to the intravenous use of drugs.