Although small non-cleaved cell lymphoma (SNCCL) is one of the more common lymphoma subtypes in children, in both Africa and the United States, it is rare in adults. Although it responds dramatically to chemotherapy in both children and adults, it is considered a high grade lymphoma in the International Working Formulation, and carries a much less favorable prognosis than does large cell lymphoma, the more common disease with which it is often grouped in treatment reports. Beginning in 1981, we treated patients with SNCCL with MCOP (methotrexate, cyclophosphamide, vincristine, prednisone) followed by IMVP-16 (ifosfamide, methotrexate, VP-16) followed by HOAP-Bleo (adri-amycin, vincristine, cytosine arabinoside, prednisone, bleomycin). From 1984 to 1988, this program was modified in that cytosine arabinoside was added to MCOP, and cyclophosphamide was substituted for ifosfamide in IMVP-16. Eighty percent of the patients entered complete remission (CR): the freedom from progression (FFP) result at five years was 60%. By multivariate analysis, Ann Arbor stage IV and age over 40 years were the most important adverse prognostic factors predicting CR and FFP results, with five-year FFP results of 24% and 40%, respectively. However, only two of the seven patients with marrow disease were free of progressive disease at five years. Central nervous system and bone marrow relapse occurred in 10 patients, nine of whom had stage IV disease, seven of whom had never attained CR. The five-year survival result was 52%, and was significantly affected by stage IV disease and age. From this study, it appears that most patients with stages I-III SNCCL may be cured with intensive therapy, and recent studies suggest that prolonged treatment is not necessary. However, patients with stage IV disease and those over the age of 40 may need early intensification with very high dose therapy in order to improve results for this subgroup.