In order to assess long-term outcome of patients with localized (stage I or II) diffuse large-cell lymphoma treated with initial combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without involved-field radiotherapy following chemotherapy, we combined data from two prospective trials in Tucson (64 patients) and Vancouver (78 patients). Follow-up on 142 patients was updated and a variety of potential pretreatment prognostic factors were analyzed for impact on outcome. One hundred forty patients (99%) achieved a complete remission and there were no differences in outcome between institutions. Twenty-three patients have relapsed and 22 have died from lymphoma at a median follow-up of 4.4 years, resulting in an overall relapse-free survival of 82% at 5 years. There was no treatment-related mortality and were no instances of late cardiac toxicity or leukemia. Of the following potential pretreatment prognostic factors (age, stage, "B" symptoms, extranodal disease, gastrointestinal tract involvement, bulky disease, or disease above or below the diaphragm), only stage affected relapse-free survival (RFS) (P = .16) and survival (.003). Among 34% of patients over age 65, outcome was similar to younger patients. RFS for 108 patients treated with CHOP plus radiotherapy was not significantly superior to the use of CHOP alone in 34 patients (P = .2).