Malignant gliomas continue to be a significant sourceof mortality in young and middle aged adults.The introduction of new treatment strategies and multidisciplinaryapproaches has improved the outcome of patients withthese tumors only slightly. Because retinoic acid hasgrowth inhibitory activity against glioma and neuroblastoma cellsin cultures, we assessed the efficacy of all-trans-retinoicacid in the treatment of recurrent cerebral gliomas.Thirty-six patients with recurrent cerebral gliomas were enteredin the study and treated with 120 or150 mg/m2/day of all-trans-retinoic acid as a singleagent. The drug was given for 3 weeksfollowed with one week of rest. Two blocksof 4 weeks constituted one course of treatment.One (3%) of 34 evaluable patients had aminor response and 14 (41%) had stable disease.In the rest of the patients (56%), tumorscontinued to progress despite treatment. The median timeto progression of all evaluable patients was 8weeks, and for the responders was 17 weeks.The higher dose level (150 mg/m2) was associatedwith high incidence of headache, which responded todose reduction. The lower dose level was verywell tolerated, with mild, mainly dermatological toxicity.All-trans-retinoic acid as a single agent has nosignificant activity against recurrent cerebral gliomas.