The chronic leukemias are associated with significant morbidity from splenic enlargement and hyperfunction. Although some patients with chronic leukemia benefit from splenectomy, the indications for operation are unclear. To identify those patients who benefit most from splenectomy, nine patients with chronic lymphocytic leukemia (CLL) and eight patients with chronic granulocytic leukemia (CGL) who had splenectomy to palliate the symptoms of massive splenic bulk or to improve the hematologic sequelae of splenic hyperfunction were studied. Splenectomy for bulk symptoms provided good palliation of symptoms, but the duration of the benefit was limited by the stage of the disease. Five of eight patients with CGL with bulk symptoms died within 6 months of operation. Splenectomy for hyperfunction was limited to a short-term hematologic response. In three of four patients with CLL who were Coombs positive, the presence of autoantibodies correlated with a recurrent transfusion requirement within 3 months of splenectomy. Thus, the benefit of splenectomy for bulk symptoms must be weighed against the risk of surgery and the patient's limited life expectancy. The benefit of splenectomy for treatment of splenic hyperfunction depends on the stimulus to hyperfunction and may not be beneficial for patients with refractory autoimmune anemias.