The hepatitis B virus (HBV) is a canny one. Acute infection is usually cleared by the immune system. But in some cases, chronic infection sets in, accompanied by integration of the virus into the nuclear DNA of liver cells. To make matters worse, HBV carriers (of which there are about 350 m) have a high risk of developing chronic liver disease (CLD) and hepatocellular carcinoma (HCC). Research into how HBV infection translates into HCC and CLD has been stymied by the lack of suitable animal models: only woodchucks, ducks and squirrels are naturally infected with related HBV-like viruses. Mark Feitelson and colleagues now describe a promising animal model in this month's issue of Nature Medicine (vol. 5, 907– 912; 1999). They engineered transgenic expression of the virus in mice with severe combined immunodeficiency. The resultant mice support HBV gene expression and replication in the liver and elsewhere (see picture for hepatocyte expression of an HBV antigen); infusing them with unprimed, syngeneic splenocytes partially clears virus from the serum and liver. Notably, the mice sustain persistent virus replication and develop CLD, but, so far, not HCC. Molecular dissection of these mice should help to identify the virus antigens and corresponding immune responses that contribute to CLD.