In wild type isolates of hepatitis B virus (HBV), the sequence of the genome may vary in up to 10% of nucleotide positions despite conservation of coding and function. Changes as small as of a single base, however, may disrupt expression of viral proteins. For example, precore mutants fail to synthesize HBeAg and point mutations in the region encoding the a determinant of HBsAg may have a profound effect on antigenicity. Investigation of HBV sequences in virus from patients with unusual serological profiles continues to reveal novel variants.