Forty chronic lymphocytic leukemia patients with splenomegaly were evaluated for splenectomy. Twenty were splenectomized. All but two normalized their hematocrit and all but one their platelet count. Satisfactory residual erythropoiesis as evaluated using ferrokinetics enabled prediction of a good response to splenectomy in 18 of 20 patients. The two patients who did not respond despite satisfactory residual erythropoiesis had a deteriorating blood count after splenectomy with progressive disease. The measurement of the splenic red cell volume predicted the minimal increase in hematocrit that could be expected after splenectomy. The transfusion need was abolished in 13 of 14 patients who needed red cell transfusions before splenectomy. Despite clinical improvement after the operation in all but two patients, splenectomized patients did not survive longer than nonsplenectomized patients, whether survival probability was calculated from the time of diagnosis or from the time of evaluation.