Patients whose lymphoma is resistant to standard treatment regimens continue to do poorly, with only an occasional patient achieving long-term remission even with bone marrow transplantation. Twenty-three patients with primarily refractory (11), or refractory relapsed (12) non-Hodgkin's lymphoma were treated with repeated cycles of dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP) without bone marrow transplantation. Each cycle of DICEP consisted of cyclophosphamide (2500 mg/m2/day, days 1-2), etoposide (500 mg/m2/day, days 1-3), and cisplatin (50 mg/m2/day, days 1-3). Twelve patients (52%) have achieved a complete response and 6 (26%)r a partial response. Three of the complete responders remain continuously free of disease for 19, 29, and 32 months, and 3 more are disease-free at 58, 59, and 65 months after receiving further therapy. Three-year survival for all patients is 45%. Patients with a good initial performance status (Zubrod 0 or 1) had a 58% complete response rate and a 2-year survival rate of 53%. One of 19 patients with an initial performance status of 0 or 1 had treatment-related mortality. Repeated cycles of DICEP can produce long-term responses in patients with refractory non-Hodgkin's lymphoma.