Six patients with Waldenström's macroglobulinemia (WM) resistant to previous 2-chlorodeoxyadenosine (2-CdA) therapy were treated with fludarabine. Both initial and subsequent therapy was administered according to the most widely used protocols. The median number of 2-CdA cycles given to the patients was 3.7 (range 2-5), while fludarabine was 1.7 (range 1-2). As a result partial remission was achieved in two patients and stabilization of the disease in the remaining four in spite of the inadequate response or progressive disease after 2-CdA therapy. Median monoclonal IgM concentration fell from 29.4 (range 11.6-37.1) to 16.4 g/l (range 3.8-29.1). At the same time hemoglobin concentration increased from median 114 (range 89-129) to 122 g/l (range 97-133). Side effects consisted of neutropenia (three patients) and thrombocytopenia (two patients). Two patients are alive with progression of the disease noted after 12 and 21 months of observation. One patient died as the result of cardiac disease, two others died of infection 5 and 16 months after cessation of therapy in the course of disease progression. The remaining patient was lost to follow-up after 10 months of observation with continuous stabilization. Our observations suggest that in WM patients resistant to 2-CdA, stabilization of the disease or even remission can be obtained with fludarabine.