Purpose: We reported previously that treatment with six cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy and 15 to 25 Gy irradiation was effective in curing children with Hodgkin's disease, but was associated with a 6.5% 10-year risk of development of secondary leukemia. Based on the results of that study, a successor study was designed with the objective to maintain treatment efficacy while decreasing adverse effects, particularly the occurrence of secondary leukemia. Patients and Methods: Fifty-seven children with a chronologic and/or bone age less than 16 years were enrolled onto this study between May 1982 and October 1990. Treatment consisted of six cycles of combination chemotherapy-three of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and three of MOPP-and low-dose irradiation (15 Gy) of involved fields. Boosts of 10 Gy were given to areas of bulky disease and to those that did not respond completely after two cycles of chemotherapy. Results: With a median follow-up duration of 6.7 years, the projected 10- year survival and event-free survival (EFS) rates are 96% (SE 2.5%) and 93% (SE 3.5%) for the entire cohort of 57 patients, and 85% (SE 10%) and 69% (SE 12.8%), respectively, for 13 patients with stage IV disease. No patient has developed a second malignancy. Growth and development have progressed normally. No patients have symptomatic cardiac, pulmonary, or thyroid disease. Subclinical abnormalities of pulmonary function were detected in 32% and chemical hypothyroidism in 16%. Conclusion: This therapy was highly efficacious in children with Hodgkin's disease without unacceptable toxicity. Future efforts should be directed toward further reducing therapy for favorable early-stage patients and improving treatment efficacy for those with stage IV disease.