Nephrogenic diabetes insipidus (DI) is characterized by inability of the kidney to concentrate urine due to diminished renal response to vasopressin. We report a patient with diabetes insipidus and hyperviscosity as presenting manifestations of Waldenstrom's macroglobulinemia. After two treatments with plasmapheresis, serum viscosity normalized and the ability to concentrate urine, polyuria, and polydipsia improved. With ongoing chemoimmunotherapy, he has not had a recurrence of DI. Although rare, nephrogenic DI is a complication of hematologic disorders such as Waldenstrom's macroglobulinemia, multiple myeloma and sickle cell anemia.