A group of athymic nude mice developed an unusual chronic wasting disease within 1-3 months after their arrival into the laboratory. Affected nude mice had severe, acute-to-chronic, active hepatitis with multinucleated giant hepatocytes and fibrosis. Vascular and central nervous system lesions were frequently present, giant cell peritonitis, ascites, and multinucleated giant cells in the intestinal epithelial villi were less frequently observed. Mouse hepatitis virus was isolated from the livers of three mice with lesions. The virus, when inoculated into nude mice, produced lesions similar to those observed in the natural outbreak.