Acute leukemia was observed to develop in three patients with Waldenstöm macroglobulinemia. Each patient had been treated with cytotoxic drug therapy. Pancytopenia preceded the onset of the terminal leukemia in two of the three cases. The acute leukemias were all of acute myelogenous type. All of the patients died soon after the development of the terminal leukemia. A number of recent reports have documented acute terminal leukemia in patients with macroglobulinemias and multiple myeloma, as well as other malignant and nonmalignant diseases. The role of the cytotoxic drugs, especially chlorambucil, cyclophosphamide, and melphalan, in leukemogenesis has been raised by these recent reports.