Two patients treated with high dose methotrexate with citrovorum rescue (HDMTX-CF) for osteogenic sarcoma developed the acute onset of neurologic deficits. Prior to the onset of symptoms, one child suffered brief episodes of altered consciousness. Both patients developed hemiparesis and then steadily improved over 72 hours. Laboratory evaluations disclosed normal coagulation parameters and nontoxic serum methotrexate levels at onset of symptoms. Computed tomography in one child disclosed a large low absorption abnormality. This patient represents the first reported case of positive radiologic findings associated with this syndrome. The two patients recovered completely and received further HDMTX-CF without sequelae. This condition may result from transient demyelination or embolic cerebrovascular disease.