We investigated the virological impact of acute hepatitis C virus (HCV) superinfection on two patients with hepatitis B virus (HBV)-related cirrhosis. In both patients, chronic HBV-infection persisted while acute HCV infection resolved spontaneously. HBV DNA was transiently suppressed in both patients but increased with HCV resolution. In Case 1 (HBeAg-positive; wild type of basic core promoter [BCP] and precore [PreC]), fluctuations of HBV DNA and HBeAg state were accompanied by mutations of the BCP and PreC. In Case 2 (HBeAg-negative; mutant type of the BCP and PreC), changes in HBV DNA levels were associated with mutations of PreC. In both cases, mutant PreC changed to the wild type upon HCV resolution, and no nucleotide A insertion at position 193 of the HCV 5'-untranslated region, which influences HCV spontaneous clearance, was detected. The putative DNA-binding motif in the HCV core was SPRG (amino acids 99-102). HCV infection was associated with changes in the nucleotide sequences of the binding site for the nuclear receptor family in HBV enhancer 2 (Enh2) including the BCP rather than Enh1. Our results suggest that the impact of acute HCV infection on chronic HBV infection varies according to HBV virological state.