All N:NIH(S)-B mice examined have multiple foci of hepatic necrosis and inflammation. The cause of hepatitis is unknown. This strain was developed at the NIH Animal Genetic Resource for use as foster mothers in the barrier facility. All mice appear clinically normal, but have significant abnormalities in their livers. Numerous studies are in progress to determine the etiology and explore the pathogenesis of hepatitis in this strain. Many mice have numerous white foci and depressions visible on liver surfaces. Microscopic foci of hepatitis and coagulation necrosis are present in all mice. Transmission EM has failed to detect any pathogens. Mouse hepatitis virus antigen is not present using immunochemistry. Lymphocyte and macrophage cell markers will be used to explore pathogenesis and identify the origin of multinucleate syncytial cells in lesions. No viruses or bacteria have yet been detected. Many mice have elevated serum enzymes indicating hepatocellular necrosis. oral and parenteral inoculation of SCID mice with fresh homogenized affected livers failed to result in transmission. Vitamin A is being examined as a possible etiology or co-factor. Mouse strains closely related to the N:NIH(S)-B are being examined for hepatic abnormalities. The cause of hepatic necrosis and inflammation in the N:NIH(S)-B mouse remains unknown. An infectious etiology is unlikely. Genetic factors appear important. Hepatitis in this mouse strain may serve as a useful model to study the pathogenesis of hepatitis in animals and humans.