Fludara I.V. (fludarabine phosphate) is a purine analogue that has been synthesized and found to have activity in lymphoid neoplasms in phase I and II studies. Fludara I.V. has been used extensively in the management of chronic lymphocytic leukemia in the last 5 years. In studies of Fludara I.V. as a single agent, the response rate was 59% in 78 patients. The true complete remission (CR) rate (no evidence of disease) was 13% with 16% having a CR with persistent lymphoid nodules. These patients are considered to be in CR using the National Cancer Institute Working Group Guidelines. The other patients (31%) achieved a partial remission (PR). Fludara I.V. has also been used as a single agent in previously untreated patients. Thirty (83%) of the 36 patients obtained a complete or partial response. Thirty-six percent of the patients achieved a true CR and 39% a CR with persistent lymphoid nodules in the bone marrow. Thus, the complete remission rate was 75%. Fludara I.V. has now been combined with prednisone in the management of 101 previously treated patients with chronic lymphocytic leukemia. Fourteen percent of patients have achieved a true CR, 24% a nodular CR, and 19% a PR. The results were very similar to those obtained with Fludara I.V. as a single agent. Other investigators have explored Fludara I.V. by continuous infusion. Twenty-two of 42 evaluable patients, in that study, achieved a PR. Fludara I.V. had minimal evidence of toxicity except for episodes of fever. The episodes of fever were more common in patients who had received previous treatment and had stage III or IV disease according to the Rai staging system. Some of these episodes of fever were associated with pneumonia. It appears that the spectrum of organisms causing the febrile episodes is that usually associated with immune deficiency (monocyte or T-cell deficiency). Future studies with Fludara I.V. will explore different schedules and combination approaches.