Chronic viral hepatitis frequently goes undetected until cirrhosis develops. Although the effect of interferon on the natural history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection in asymptomatic persons is unknown, treatment may modify the course of the infection, producing cures in some. In September 1992, screening for HBV and HCV was offered in 40 centers throughout the United States. Demographic features, potential risk factors, and symptoms were studied. Blood samples were obtained for the determination of serum alanine aminotransferase levels and for markers of HBV and HCV infection. Thirteen thousand nine hundred ninety seven subjects were screened. The prevalence of infection with HBV or HCV was 24.8% (HBV 17.8%; HCV 7.0%; and both 2.8%). Hepatitis B and C disease was present in 0.7% and 4.4% of the population, respectively. Risk factors for HBV and HCV infection were similar in: blood transfusions, hemodialysis, IV drug use, and sex with an IV drug user. For HBV infection, sex with multiple partners, increasing age, and birth in South East Asia or Africa were additional risk factors. The cost to find a case of HCV infection is less than the costs for finding many other treatable diseases. Screening for HBV, though more costly, is reasonably efficient, and simultaneous screening for HBV and HCV provides greater efficiency. It is practical to consider screening for HBV and HCV in the United States, particularly if any risk factor is present. Improved treatment strategies will make screening even more cost effective.