From 1978 to 1982, 28 children with localized non-Hodgkin's lymphomas, stages I and II, were treated with a combined modality protocol, reduced in intensity in comparison to our previous institutional protocol (1975-1978, reported in Cancer 45: 630-637, 1980), and modest by comparison to many current intensive regimens in widespread use. Induction consisted of vincristine (6 weekly doses, 1.5 mg/m2), cyclophosphamide (3 doses, on days 0, 21, and 42, 600 mg/m2 IV), and oral prednisone (40 mg/m2, daily for 1 mo) combined with low-dose, involved-field, supervoltage radiotherapy (2000 rads). Prophylactic treatment of the central nervous system was not given to all children, but only to those with primary tumors in the head and neck region, and consisted of intermittent intrathecal methotrexate only (12 mg/dose, three times in induction, and subsequently every 6 wk). Maintenance therapy, consisting of oral daily 6-mercaptopurine (75 mg/m2) and oral weekly methotrexate (30 mg/m2), was continued for a total duration of 15 mo from diagnosis. Overall, there were 15 children with stage I and 13 with stage II disease, and the majority of the cases (17 of 28) were localized to the head and neck. In addition, 7 children, all stage II, had completely resected gastrointestinal tumors; the other 4 cases presented in inguinal nodes. Histologically, 27 of the 28 tumors were high-grade diffuse (13 undifferentiated, i.e., small noncleaved cell type; 11 histiocytic, i.e., 5 large noncleaved cell type, and 6 immunoblastic type; and 3 lymphoblastic type); 1 case was mixed cell type, nodular and diffuse. All children were judged to be in complete remission at the end of induction, and 24 of 28 (85.7%) remain free of disease 4+ mo to nearly 4 yr from diagnosis (median 24+ mo); 19 have completed all planned therapy and are in unmaintained remission. The 4 cases failing therapy all were characterized by diffuse undifferentiated (small noncleaved cell) histology and exhibited regrowth of local tumor, resulting in a failure rate for this group (4 of 13, 30%) significantly different than for all remaining cases of other histologies (0 of 15), p less than 0.02 by log rank analysis. Patient tolerance to therapy was excellent, with negligible acute toxicity, and ambulatory outpatient management was the norm. Long-term follow-up will be necessary to judge whether adverse late consequences of treatment have been reduced by this approach. We conclude that a reduction in the intensity of therapy for children with stage I and II non-Hodgkin's lymphomas is feasible, apparently without significantly jeopardizing their excellent chance for cure.