The aim of the present study was to evaluate the feasibility and efficacy of the intensified induction chemotherapy regimen ACOMED for patients with aggressive non-Hodgkin's lymphoma (NHL). Untreated adult patients with aggressive NHL, presenting with Ann Arbour stage II-IV disease or stage I with bulky disease, and with at least one of the following risk factors: age > 60 years, advanced disease, elevated serum lactate dehydrogenase level, Eastern Cooperative Oncology Group (ECOG) performance status >or= 2, presence of extranodal sites of disease and bulky disease, were treated with the ACOMED regimen consisting of 4-6 cycles of adriamycin 25 mg/m(2) i.v. on days 4-5, cyclophosphamide 250 mg/m(2) i.v. on days 1-5, vincristine 2 mg i.v. absolute on day 1, methotrexate 500 mg/m(2) i.v. on day 1 with leucovorin-rescue after 24 h 30 mg/m(2) i.v. and 3 x 15 mg p.o., etoposide 100 mg/m(2) i.v. on days 3-5, dexamethasone 10 mg/m(2) p.o. on days 1-5 and granulocyte colony-stimulating factor support, repeated on day 21. Twenty-two patients were treated within this study at a single center. After 4-6 cycles of ACOMED followed by additional involved field radiotherapy in 18 patients, the complete and overall response rates were 86% (19 of 22 patients) and 95% (21 of 22 patients), respectively. After a median observation time of 10 years and 2 months, 16/22 (73%) patients are alive in continuous complete response without evidence of any late toxicities. ACOMED followed by involved field radiation presents a highly effective regimen for remission induction and long-term survival in patients with aggressive NHL, and merits further investigation.