Liver toxicity, although not mentioned among the possible adverse effects of corticosteroids, has been occasionally reported in literature. We observed 2 cases of hepatotoxicity after a high-dose methylprednisolone treatment of a demyelinating disease and evaluated the potential relationship in the light of available evidence. The first patient developed a histologically documented acute hepatitis and recovered after 3 weeks. In the second patient, a mild augmentation of liver enzymes occurred, followed by normalization in a few days. The causal relationship between hepatotoxicity and methylprednisolone treatment was deemed probable in both cases. Careful review of the literature suggests that corticosteroid-induced liver damage may be more frequent than commonly believed.