Hepatitis B virus (HBV) mutants have recently been identified in patients with acute and chronic HBV infection. They accumulate during the natural course of infection and may eventually constitute the major or only viral species. Mutations have been detected in all viral genes (except the X-gene) and may be associated with a specific clinical course of the infection, e.g., chronic active or fulminant hepatitis. The exact contribution of mutations to the natural clinical course of HBV infection remains to be established, however.