Medulloblastomas are among the most common malignant brain tumors in children. These tumors consist of immature bipotential cells that may differentiate into neuronal and glial cells. We have established two cell lines for human medulloblastoma. One was derived from a 2-year-old girl with a cerebellar tumor (designated as ONS-76) and another from a 9-year-old girl with a metastatic tumor in the right frontal lobe (ONS-81). The in vitro population-doubling times were 18.6 and 19.2 h, respectively. Immunohistochemical studies showed that both cells possessed neurofilament protein (Mr 145,000 and 200,000) and neuronspecific enolase, without glial fibrillary acidic protein or S-100 protein. Human γ-interferon enhanced class I major histocompatibility complex antigens on these medulloblastoma cells. Class II major histocompatibility complex antigens were also induced by human interferon-γ. We here report for the first time the expression of class II major histocompatibility antigens, which play an important role in immune response, on human medulloblastoma cells with neuronal differentiation.