AIMS To probe the effect of interferon in combination with rib- avirin on the plus and minus strands of hepatitis C virus RNA (HCV RNA). METHODS Twenty-three cases diagnosed as chronic hepatitis C (CHC) according to positive HCV RNA/anti-HCV,fluctuating levels of aminotransferase activities (>1 year) and absence of other hepatitis virus marker,were studied. Among them,13 pa- tients received combined antiviral therapy (subcutaneous injection of 3MU of interferon-α three times per week for 3 months and intra- venous drip of 1 g of ribavirin per day during the first month of treatment with interferon) and 10 patients received single interfer- on therapy (the same as above-mentioned) as control. The plus and minus strands of HCV RNA in sera and peripheral blood mononuclear cells (PBMCs) of these patients were tested by means of nested reverse transcription-polymerase chain reaction (nested RT-PCR). RESULTS At the end of therapy,the abnormal ALT levels de- creased to normal range in 9 (69.23%) cases in the combined antiviral group. Of them,5 (55.56%)experienced post-therapy relapse and 4 (44.44%) were complete responders. In the inter- feron group,the ALT decreased to normal in 6 (60%) cases,of which,4 (66.67%) had post-therapy relapse and 2 (33.33%) were complete responders. The differences between the two groups were nonsignificant (P>0.05). At the end of therapy,the positive rate of the plus strand in sera decreased from 92.3% to 38.46% (P<0.05) and that of the minus strand in PBMCs,from 76.92% to 38.46% (P<0.05) in the combined antiviral group; and in the interferon group,the former decreased from 100% to 50% (P<0.05) and the latter,from 90% to 40% (P<0.05). Again,no significant differences were found between groups (P >0.05). The relapse occurred in patients whose plus strand HCV RNA in PBMCs remained positive before and after treatment. CONCLUSIONS Ribavirin could not enhance the antiviral effect of interferon. The absence of HCV RNA in serum does not mean complete clearance of HCV,and its value for evaluating