The activity of fludarabine monophosphate (FLU) and alpha-interferon (alpha-IFN) in low-grade non-Hodgkin's lymphoma (LG-NHL) and B-cell chronic lymphocytic leukemia (B-CLL) has been demonstrated in several clinical trials. In a study of 137 previously treated patients, of whom 77 had B-CLL and 60 with LG-NHL, we used FLU as salvage chemotherapy. Dosages of 25 mg/m2 were given in 30-min infusions for 5 consecutive d. Treatment was repeated every 28 d depending on the patient's clinical status for a maximum of 6 cycles. Entrance to the alpha-IFN maintenance portion of the study depended on patient response to initial FLU. All patients who had obtained a complete or partial response after the FLU therapy were randomized to receive alpha-IFN or no further therapy. The alpha-IFN dose was 3x10(6) units 3 times per wk until disease progression. At 4 yr with a median follow-up of 22 months the percentage of patients with persistent response ranged between 20% and 30% among all the responders. Thirty-five (45%) B-CLL patients achieved major responses (complete/partial response), as did 29 (48%) of those with LG-NHL. Among the 64 patients who achieved a good response to initial therapy and who have entered the second part of the trial, there has been a rate of prolongation of remission in favour of maintenance alpha-IFN (p=0.02). FLU therapy is an effective drug inducing remission in pretreated B-CLL and LH-NHL patients. However, as with other therapeutic modalities, remission is rarely maintained beyond 2 yr. So far, maintenance alpha-IFN has not been shown to produce significantly longer remission after treatment with FLU in LG-NHL, and there is no trend towards prolonged remission in B-CLL patients. The role of FLU needs to be further evaluated in the management of lymphoproliferative disorders by introducing it in combination with other drugs (alpha-IFN) in the induction phase and in maintenance treatment.