Twenty-three patients with refractory, aggressive-histology, non-Hodgkin's lymphomas were treated with cytosine arabinoside (2.0 g/m2 i.v. every 12 h on days 1 and 2), etoposide (100 mg/m2 i.v. on days 1 and 2), and cisplatin (35 mg/m2 i.v. on days 1 and 2) every 3 weeks. All patients had received one or two prior chemotherapy regimens. Five of 19 (26%) evaluable patients responded, with a median duration of response of 9 weeks (90% confidence interval: 11-48%). One patient with a complete response remains free of disease over 31 months after completing six cycles of therapy. Six transient responses of less than 1-month duration were also observed. Hematological toxicity was significant: 73% of patients experienced grade 4 neutropenia, and 52% experienced grade 4 thrombocytopenia. Twenty patients (87%) underwent dose reductions following their first cycle of therapy for grade 3 or 4 myelosuppression. We conclude that this combination of drugs, when administered by this schedule, has limited antitumor activity; however, administering the regimen with a dose-intense schedule appears warranted.