The prognosis of patients with refractory or relapsed malignant lymphoma is poor. To improve the outcome of such patients, a therapeutic regimen of VIM +/- B (etoposide/ifosfamide plus mesna/methotrexate/ with or without bleomycin) was administered. Of 47 patients treated, 15 had relapsed following complete remission (CR) after first-line chemotherapy, 28 had failed to achieve CR with first-line therapy, and four failed to respond to multiple salvage regimens. All patients had received extensive prior chemotherapy, and 36 had received combinations containing doxorubicin. Eight patients had low-grade non-Hodgkin's lymphoma (NHL), 28 had high-grade NHL, and 11 patients had Hodgkin's disease. Overall response rate was 87%, with 45% CR and 42% partial remission (PR). Median relapse-free interval was 8 months in patients with CR and 6 months in those with PR. Of patients with CR, 43% were predicted to be without relapse at 2 years and 31% at 5 years. Median survival time for all patients treated with 14 months-22 months for those with CR and 10 months for those with PR. Probability of survival at 2 years was 30% in all patients, 50% in patients with CR, and 15% in those with PR. VIM +/- B appears to be effective against refractory or recurrent lymphoma, resulting in response in a large number of patients and long-term survival and possible cure in a small but significant number. Results indicate that VIM +/- B is particularly effective in patients with high-grade NHL who have responded suboptimally to primary therapy.