Burkitt's lymphoma in Africa may be curable by chemotherapy alone; in nonendemic regions results are reportedly less favorable. Fifty-four Americans with Burkitt's lymphoma were treated with two sequential combined treatment regimens that incorporated therapeutic approaches from clinical trials in Africa. Four patients died during induction therapy, and 48 of the remaining 50 achieved complete remissions. Twenty-two relapsed at a median of three months from the start of therapy. The overall two-year actuarial survival was 54 percent: younger patients ( less than 12 years old) and patients with minimal tumor burden (stages A, B and AR) had significantly better survivals than older patients (P less than 0.02) and patients with advanced abdominal tumors (stages C and D) (P less than 0.01). No differences in survival were detected between patients treated at the National Institutes of Health and those treated in regional institutions on either protocol. Complete response rates, relapse frequency and survival in American patients are similar to results in Africa.