Seventeen extensively pre-treated patients with non-Hodgkin's lymphoma in relapse were treated with high-dose cytosine arabinoside given at a dose of 3 g/m2 on a 12-hour basis for two to eight doses per course. Seventy percent of patients (12 of 17) showed response with this regimen, including three patients who achieved a complete response. The time to response was quite rapid, occurring between three and 14 days, with median duration of complete responses of 12 weeks and of all responses, five weeks. Toxicity was acceptable, including predictable myelosuppression and thrombocytopenia, occasional drug fever, infrequent conjunctivitis and dermatitis, and no central nervous system toxicity. The dramatic, albeit short-lived, responses to high-dose cytosine arabinoside in this refractory population suggest that it is an active agent against non-Hodgkin's lymphoma and should be further evaluated.