In this study, we evaluated the efficacy of fludarabine (FLU), an adenine nucleoside analogue, in 35 previously treated patients with advanced and progressed B-cell chronic lymphocytic leukemia (B-CLL) and in 6 at diagnosis. All patients were treated at a dose of 25 mg/m2 per day for 5 consecutive days (mean number of courses was 5, with a range from 4 to 6). The majority of patients experienced a beneficial effect on hematological parameters. In particular, a remarkable reduction of lymphocyte count together with an increase of neutrophils and platelets was observed. The overall response rate was 42% with 1 complete response and 16 partial responses. Ten patients achieved minor responses and the remaining 14 showed no benefit from treatment. An increased response rate was achieved in 6 untreated patients who showed an overall response rate of 67% (4/6). The major complications observed were neutropenia (66%) and febrile episodes (44%) that were generally infection-related and were fatal in 3 cases. Because we were dealing with patients whose disease was advanced and/or resistant to treatment, the overall results may be considered encouraging with acceptable toxic reactions not superior to those frequently observed with polychemotherapy.