We determined the core region nucleotide and amino acid sequences in specimens from two patients with chronic hepatitis C during intervals of normal and elevated alanine aminotransferase (ALT) concentrations. When the ALT concentrations remained normal, the serum HCR-RNA concentration exceeded that before therapy and most of the clones that could be sequenced had a deletion or an amber mutation. The clones isolated from a HLA B44-positive patient had a mutation at amino acid 91. These results suggest that expression of the wild-type HCV core region genome may be associated with liver cell damage.