Ninety patients with progressive recurrent lymphoma were treated with a combination of cisplatin 100 mg/m2 intravenously (IV) by continuous infusion over 24 hours, followed by cytosine arabinoside in two pulses each at a dose of 2 g/m2 given 12 hours apart. Dexamethasone, 40 mg orally or IV, was given on days 1 through 4. Vigorous hydration was reinforced by routine use of mannitol. Treatments were repeated at 3- to 4-week intervals for six to ten courses. Most patients had not achieved complete remission (CR) with prior therapies, which included Adriamycin (all patients) and methotrexate and VP-16 (58 patients). Median patient age was 55 years. Intermediate-grade lymphoma was the most frequent pathologic diagnosis. Seven patients died within two weeks of therapy; of the remaining 83 patients, 28 (34%) or 31% if all patients are considered, achieved CR, and 22 (26.5%) achieved partial remission (PR). Response was evident after the first two cycles of chemotherapy and appeared to be independent of the histopathologic type of lymphoma. To date, only eight of the complete responders have relapsed at a median follow-up of 11 months. The overall 2-year survival in 25%. Further analysis showed that patients with low tumor burden and normal lactic acid dehydrogenase (LDH) had a high CR response rate (67%) and a survival rate of 61% at 2 years. In contrast, patients with both high tumor burden and elevated serum LDH levels had a negligible CR rate, and only 5% are surviving at 1 year. Patients with either high tumor burden with normal LDH or low tumor burden with elevated LDH had an intermediate survival. Myelosuppression-related infection was the most frequent serious complication of this regimen (31%) and the cause of death of ten patients. Acute lysis syndrome was also observed in five patients with high tumor burden and was the cause of death in three of these patients. DHAP has proven to be an effective non-crossresistant regimen for patients with relapsing or refractory lymphoma, particularly for patients who have favorable prognostic characteristics.