A controlled clinical study in children with lymphoblastic leukemia was conducted to measure the potential benefit of time sequencing vincristine and cyclophosphamide. Vincristine and cyclophosphamide were utilized in a maintenance regimen in children after a remission had been obtained. Patients received vincristine either 24 hours before cyclophosphamide or simultaneously with cyclophosphamide. The median time to relapse and the number of continued remissions was significantly increased for patients receiving vincristine 24 hours before cyclophosphamide when compared to those patients receiving both drugs simultaneously. The results of this comparative study indicate that the sequential use of vincristine and cyclophosphamide for maintenance of a second relapse in childhood ALL produces a greater duration of remission than when both are used simultaneously.