Historically, the survival of children and adolescents with Burkitt's and Burkitt-like lymphoma had been poor. Recently, short and intensive chemotherapy appears to have improved disease outcome. We therefore reviewed the results of four successive Children's Cancer Group trials conducted on 470 children with disseminated Burkitt's and Burkitt-like lymphoma. Of the patients studied, the median age was 8 years (0-21 years), the male:female ratio was 4:1, 58% had lactate dehydrogenase (LDH) > or = 500 IU/l, 23% had M2 or M3 bone marrow (BM), and 12% demonstrated central nervous system involvement. In a multivariate analysis, the 4-year event-free survival (EFS) in patients > or = 15-years-old compared with < 15-year-old was 34 +/- 7 versus 59 +/- 2% (P < 0.05), the 4-year EFS of M2/M3 compared with M1 BM was 38 +/- 5 versus 63 +/- 3% (P < 0.001), and the 4-year EFS with LDH > or = 500 IU/l compared with LDH < 500 IU/l was 49 +/- 3 versus 71 +/- 4% (P < 0.001). Furthermore, patients treated on the most recent protocol, which was short and more intensive, had a significantly improved survival compared with those on previous trials (4-year EFS 80 +/- 6 versus 54 +/- 2%, P < 0.001). In summary, the outcome for childhood Burkitt's and Burkitt-like lymphoma has recently improved with the use of short and intensive B-cell non-Hodgkin's lymphoma-directed therapy.