Although hepatitis C virus (HCV) infection is the most common chronic blood-bome infection in the United States, the annual incidence of new infections has decreased by more than 80% since 1989 to approximately 36,000 new infections by 1996. The Third National Health and Nutrition Examination Survey (NHANES III) revealed that an estimated 3.9 million US citizens (1.8%) have been infected with HCV. Of these, approximately 2.7 million persons are chronically infected with HCV. Population-based studies indicate that 40% of chronic liver disease is HCV related. Chronic hepatitis C results in an estimated 8,000 to 10,000 deaths each year. Because the prevalence of HCV infection is approximately threefold higher among persons now between 30 and 49 years of age, the number of deaths resulting from HCV-related liver disease could increase substantially during the next 10 to 20 years, as this cohort reaches the ages at which complications from chronic liver disease typically occur. Most people who develop chronic infection may not even be aware that they have been infected, because acute disease is commonly benign. However, infected persons can transmit the disease to others and are at risk for developing chronic liver disease. HCV is transmitted primarily through direct percutaneous exposures to blood. In the United States, blood transfusion accounted for a substantial proportion of HCV infections before 1990, when routine testing began, but now accounts for only a small percentage. Injection drug use is currently the major risk factor for acute HCV infection. Prevention and control of HCV infection in the United States must focus not only on reduction of transmission in groups at high risk of infection (e.g., injection drug users) but also on the early identification of persons with chronic infection.