Hepatitis B virus has been considered to be strictly organotropic and to infect and multiply only the hepatocytes of humans and chimpanzees. The localization of hepatitis B surface antigen in extrahepatic tissues has been regarded as due to deposition or phagocytosis of hepatitis B surface antigen circulating in the blood. In the present study, however, we demonstrated hepatitis B virus antigens in the pancreases of autopsied subjects with hepatitis B surface antigenemia by Shikata's orcein stain, and immunoperoxidase, immunofluorescent studies; hepatitis B surface antigen and hepatitis B virus core antigen were localized within the cytoplasm of pancreatic acinar cells in 18 and 6 cases, respectively, out of 30 cases studied. In contrast, 25 autopsy cases with no hepatitis B surface antigenemia failed to stain hepatitis B surface antigen or hepatitis B core antigen in the pancreas and liver. Therefore, it may be reasonable to assume that hepatitis B virus can infect and replicate in the human pancreatic acinar cells; however no convincing hepatitis B virus-associated ultrastructures were detected in the present study. Although there were some cases demonstrating chronic inflammatory reaction or fatty necrosis, or both, in the pancreas with hepatitis B virus antigens, the causal relationship between these pathologic changes and hepatitis B virus infection awaits further clarification.