Temporary neurologic abnormalities were detected in 9 of 60 patients undergoing treatment with high-dose methotrexate and citrovorum factor rescue (MTX-CF) for osteosarcoma. The incidence of abnormalities and abnormalities themselves were more severe than previously reported. This was attributed to an increased dose and more frequent administration of MTX-CF. In view of the transient nature of the abnormalities, a biochemical cause is implicated, and the mechanisms by which it may occur are discussed.