To evaluate the effect of interferon-alpha treatment on the levels of serum aminotransferase (sALT) and of hepatitis C virus (HCV)-RNA, we studied 19 patients with chronic non-A, non-B (NANB) hepatitis. Before therapy, 14 patients were positive by nested polymerase chain reaction (PCR) with primers deduced from the 5'-non-coding region of the HCV genome. Serum HCV-RNA had disappeared in 12 (85.7%) of them by the end of therapy, but then reappeared 6 months later in 4 of these 12 patients. A marked improvement in sALT was seen in 5 of the 8 patients with sustained HCV-RNA disappearance, but not in the 4 patients with only transient HCV-RNA negativity. Pre-treatment levels of hepatitis C viremia, analyzed by single PCR and dot blot hybridization, ranged from 2.10(3) to 2.10(8) copies/ml, and were below 2.10(5) copies/ml in patients with a complete response to interferon therapy. These results suggest that this HCV-RNA assay, combined with sALT testing, may be useful for estimation of the long-term efficacy of interferon therapy in hepatitis C.