Patients with non-Hodgkin's lymphoma (NHL) who fail to respond to first-line treatment or relapse after having shown complete or partial remission have a poor prognosis, especially in high-grade NHL. Several salvage regimens show considerable toxicity and a poor long-term outcome. In this retrospective study we analyzed data of 55 patients (34 men and 21 women) with a median age of 66 years (range: 18-89). The combination chemotherapy (VIM) consisted of VP-16 (etoposide) 65 mg/m2, ifosfamide 650 mg/m2 and mitoxantrone 3 mg/m2 and was administered on 3 consecutive days along with mesna as uroprotection. Patients were treated for refractory disease or relapse and did not qualify for high-dose chemotherapy and ABMT. Stages according to the An Arbor classification were: stage I/16, II/4, III/8 and IV/37 patients. Thirty-three patients suffered from high-grade and 22 from low-grade NHL. Toxicity (WHO recommendations) was very mild. High-grade NHL showed a better response rate (18/33, 46%) than low-grade NHL (7/22, 36%). Overall response was 41% (12 CR and 11 PR) with a median duration of 36 months (range: 6-57 months). The combination therapy investigated exhibits mild toxicity even in extensively pretreated or elderly patients. The overall response rate of 41% might be improved by increased dosage and growth factor support.