The kinetics of HCV during interferon (IFN) therapy have recently been described and the estimated virion half-life is an average of 2.7 h, suggesting that HCV infection is highly dynamic. The aim of this study was to evaluate serum levels of HCV-RNA and HCV core protein (HCV-AE) before and after incubation at 37 degreesC for 24 h. We also evaluated the viral kinetics during IFN treatment by determining their serum levels at 0, 24 and 48 h, and day 8 after the start of treatment. The decay slope was calculated as the logarithm of the ratio of HCV-RNA levels at 0 and 24 h of incubation: log(virus load) 24 h-1og(virus load) 0 h and the estimated half-life was also calculated. The decay slope was - 1.66 +/- 0.75 (- 4.12 to - 0.18) (mean +/- S.D. (range)) and the estimated virion half-life was 6.2 +/- 6.9 h (1.8-39.3). The HCV-RNA level was rapidly decreased to 6.8 +/- 13.1% of the initial load after incubation independently of the serotype. In contrast, the HCV-Ag level after incubation for 24 h was 98.7 +/- 12.2% of the initial level. The synthesized naked HCV-RNA (equivalent to 10(7) copy/ml) was not detected after 1-min incubation. These data suggested that HCV virions are very unstable and collapsed rapidly and that HCV-RNA, existing outside of virions, is immediately degraded in serum, whereas HCV-Ag remains stable. IFN treatment caused a rapid decrease in the levels of both HCV-RNA and HCV-Ag. The HCV-RNA decay slope was - 1.95 +/- 0.96 (range: - 3.48 to - 0.50) and was similar to that seen in the incubation study. Our result suggested the significance of measuring HCV-Ag during clinical management independently of HCV-RNA, especially because of its high stability. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.