A clinical or subclinical leukoencephalopathy occurs in some children after treatment of acute lymphatic leukemia with prophylactic cranial radiation therapy and parenteral or intrathecal methotrexate. We have observed a similar clinical leukoencephalopathy in patients with bone tumors treated with intravenous high-dose methotrexate and citrovorum factor without cranial irradiation. CT scans of such patients may indicate decreased white matter attenuation, but visual appraisal of this phenomenon is occasionally misleading. A computerized method for analyzing white matter hypodensity by determining the mean attenuation coefficient for one or several contiguous CT slices has therefore been developed. Serial comparisons of this mean attenuation coefficient appear to be more reliable than simple visual appraisal.