We studied the role of an "early" 4-month course of interferon therapy on posttransfusion viral hepatitis C (PTH-C). Paired serum samples of 51 consecutive recipients, taken before and 7-20 days after blood transfusion, were prospectively tested for hepatitis C virus ribonucleic acid (HCV RNA) using the polymerase chain reaction assay. Seven recipients experienced seroconversion of HCV RNA after transfusion. Two of the seven patients underwent an early 4-month course of interferon alpha therapy at a dose of 3 mU per day for 5 days during the first week, then three times a week for the subsequent 15 weeks. The first patient was treated at a very early stage of acute PTH-C and responded well to interferon therapy. Acute PTH-C in the second patient was prevented by interferon therapy. Both patients had normal serum alanine aminotransferase levels and tested negative for anti-HCV and HCV RNA 12 months after the end of treatment. Four of the five patients not on interferon therapy developed abnormal serum alanine aminotransferase activities more than five times the normal upper limit (383 +/- 143 IU/L) at 2-18 weeks after transfusion. All four patients experienced seroconversion of anti-HCV, and three patients developed chronic hepatitis. This study suggests that early long-term interferon therapy has the potential to prevent PTH-C.