We designed a protocol that included 2 months of intensive Cytoxan (cyclophosphamide; Bristol-Myers Co, Evansville, IN), high-dose methotrexate (MTX), high-dose cytarabine (ara-C), and vincristine (HiC-COM) to improve event-free survival (EFS) for patients with advanced-stage Burkitt's lymphoma and B-cell acute lymphoblastic leukemia (ALL). We also wished to test the feasibility of rapidly cycling Cytoxan and high-dose ara-C based on signs of early marrow recovery. Twenty patients including 12 with stage III Burkitt's lymphoma and eight with stage IV Burkitt's lymphoma or B-cell ALL were entered onto this pilot study. The rate of complete remission was 95%. Four patients have relapsed. The 2-year actuarial EFS was 75% (median follow-up, 37 months). Two of the initial five patients developed transverse myelitis, which we believe may have been secondary to the concomitant administration of intrathecal (IT) and high-dose systemic ara-C. We conclude that this short but intensive regimen is highly effective for patients with advanced Burkitt's lymphoma and B-cell ALL. EFS has improved over previous less intensive regimens, and is comparable to regimens of longer duration.