Purpose: The management of early-stage Hodgkin's disease in the United States is controversial. To evaluate whether staging laparotomy could be safely avoided in early-stage Hodgkin's disease and whether chemotherapy should be a part of the treatment of nonlaparotomy staged patients, a phase III intergroup trial was performed. Patients and Methods: Three hundred forty-eight patients with clinical stage IA to IIA supradiaphragmatic Hodgkin's disease were randomized without staging laparotomy to treatment with either subtotal lymphoid irradiation (STLI) or combined-modality therapy (CMT) consisting of three cycles of doxorubicin and vinblastine followed by STLI. Results: The study was closed at the second, planned, interim analysis because of a markedly superior failure-free survival (FFS) rate for patients on the CMT arm (94%) compared with the STLI arm (81%). With a median follow-up of 3.3 years, 10 patients have experienced relapse or died on the chemoradiotherapy arm, compared with 34 on the radiotherapy arm (P < .001). Few deaths have occurred on either arm (three deaths on CMT and seven deaths on STLI). Treatment was well tolerated, with only one death on each arm attributed to treatment. Conclusion: These results demonstrate that it is possible to obtain a high FFS rate in a large group of stage IA to IIA patients without performing staging laparotomy and that three cycles of chemotherapy plus STLI provide a superior FFS compared with STLI alone. Extended follow-up is necessary to assess freedom from second relapse, overall survival, late toxicities, patterns of treatment failure, and quality of life.