Current treatment for stage IIIA Hodgkin's disease consists of total nodal radiation therapy or a combination of radiation therapy (RT) and chemotherapy. In most series, 50%-65% of stage III2A patients receiving RT alone have a 5-year disease-free survival (DFS); when chemotherapy is added to RT, the percent of patients having a 5-year DFS is increased to 76%-89%. At the University of Chicago we have identified prognostic subgroups of patients, based on the extent of abdominal disease. Pathologic substage III2A patients treated with total nodal RT alone have a significantly lower 5-year DFS rate (54%) than do IIIA patients treated with combined-modality therapy (100%; P = 0.015). Pathologic substage III1A patients in the two treatment groups show no significant differences in 5-year DFS (P = 0.69). Given the potential for long-term morbidity following combined-modality therapy, we recommend that careful pathologic staging be used to determine which patients would benefit most from RT plus chemotherapy. Future treatment programs must be designed to minimize chronic morbidity while maintaining or improving cure rates.