A 50-year-old man with large granular lymphocytic leukemia (CD3+, CD8+) complicated by severe pancytopenia and life-threatening infections refractory to therapy with prednisone, methotrexate, cyclosporine, and G-CSF is described. Treatment with two cycles of 2-chlorodeoxyadenosine (2-CDA) at 0.1 mg/kg by continuous intravenous infusion for 7 days each cycle resulted in resolution of cytopenias and clearance of leukemic cells. T-cell receptor gene rearrangement, initially present, was not detectable after therapy with 2-CDA. The rapid and complete response to 2-CDA after unsuccessful attempts with prior therapy suggests that 2-CDA should be considered for initial treatment of this disorder.