A natural outbreak of mouse hepatitis virus infection developed in a breeding colony of nude mice in Taiwan. The outbreak was unique in that morbidity was high in both adult and suckling mice, but only sucklings died. In contrast, all suckling heterozygous (nu/+) mice survived, and no lesions were found in adult female heterozygous (nu/+) mice. Adult male nude mice had chronic, active, necrotizing hepatitis with syncytial giant cells, but no lesions were detected in other tissues. Immunohistochemistry with anti-A59 and anti-JHM serum revealed mouse hepatitis virus antigen in the liver of infected adult and suckling nude mice, although less intensively in the kidney of adult nude mice. Suckling BALB/c mice inoculated with filtrates of the liver of adult nude mice developed hepatitis similar to that in the naturally infected nude mice. Virus was isolated by inoculating cell-free liver filtrate from infected adult nude mice onto 3T3 cells. Electron microscopy of purified virus revealed 100-nm-diameter enveloped particles with characteristic petal-shaped surface projections. We conclude that the outbreak was caused by a weakly virulent, highly hepatotropic murine hepatitis virus.