To establish the effect of interferon alpha-2B (IFN-alpha) treatment on hepatitis C virus (HCV) viremia, rather than monitor the alanine aminotransferase (ALAT) values we measured HCV-RNA by cDNA-polymerase chain reaction (cDNA-PCR) in plasma before and during IFN-alpha treatment. Eight hemophilia patients with chronic hepatitis C were treated with IFN-alpha for 24 weeks: 5 MU daily for 2 weeks, 2.5 MU daily for 4 weeks, and 1.5 MU three times a week for 18 weeks. HCV-RNA, as measured by cDNA-PCR, was present in all patients before treatment. After 24 weeks of treatment HCV-RNA was no longer detectable in three of eight (37.5%) patients, whereas only one of eight (12.5%) patients showed complete ALAT normalization. In three of eight patients a transient response to IFN-alpha was seen, with renewed HCV-RNA detection after dose reduction. HCV-RNA measurement by cDNA-PCR appeared to be more sensitive in detecting relapse than ALAT measurement.