A study was carried out to assess the correlation between the serum concentration of hepatitis C virus RNA (HCV-RNA) in patients with chronic hepatitis, as measured by competitive reverse transcription polymerase chain reaction (cRT-PCR) and branched DNA probe assay (bDNA), and response to interferon-alpha (IFN alpha) therapy. The serum HCV-RNA concentration was evaluated by both cRT-PCR and bDNA in 54 patients who had received a total dose of 480 MU of IFN alpha. HCV subtypes were also identified in all patients. The measurement of serum HCV-RNA concentration by bDNA correlated significantly with that of cRT-PCR. The concentration of HCV-RNA in subtype 1 patients was significantly higher than that in subtype 2 patients when measured by bDNA, but not when measured by cRT-PCR. The correlation of HCV-RNA concentration between bDNA and cRT-PCR was associated with both subtypes 1 and 2. The difference in serum HCV-RNA concentration between complete and incomplete responders was more significant when measured by bDNA probe assay than by cRT-PCR. Moreover, only 1 of 26 patients with a HCV-RNA concentration of more than 1 x 10(6) eq/ml as measured by bDNA probe assay attained a complete response, while 19 of 28 patients with that of less than 1 x 10(6) eq/ml achieved it. Measurement of serum HCV-RNA concentration by bDNA probe assay was a better predictor of clinical response of IFN alpha therapy than measurement by cRT-PCR.