Twenty-seven evaluable children with early first bone marrow relapse of acute lymphoblastic leukemia were treated with an intensive induction/consolidation and ongoing maintenance therapy. Induction therapy consisted of a 35-day course of daunomycin, vincristine, and prednisone, immediately followed by teniposide, cytosine arabinoside (Ara-C), and L-asparaginase. Intrathecal methotrexate, hydrocortisone, and Ara-C were given through the induction/consolidation phase. Twenty-three of 27 patients achieved remission by the end of induction/consolidation. Maintenance with the same drugs in a modified dosage schedule continued for approximately 2 years. A small subgroup of patients who were M3 at day 35 but M1 at day 56 (end of induction/consolidation) and had a cumulative event-free survival (EFS) of only 0.40 at 6 months, all had relapsed by 15 months. However, the EFS for M1 patients by day 35 and maintained on chemotherapy was 0.64 at 12 months and 0.32 at 30, 36, and 48 months, respectively. Although good reinduction and remission duration rates at 12 to 24 months were achieved and an apparent plateau in survival occurs at 30 months, fall-off in survival would not be unexpected with probably less than 20% alive after 5 years.