A hypersplenic syndrome developed in a group of 15 chronic hemodialysis patients. Splenectomy eliminated or reduced the need for routine transfusion requirements; granulocytopenia, lymphocytopenia and thrombocytopenia were corrected. Following renal transplantation azathioprine therapy was tolerated in the splenectomized group. One patient who refused splenectomy had persistent severe leukopenia. Spleens were normal to moderately increased in weight and contained an immunoreactive white pulp and a normal red pulp though increased hemosiderin was sometimes present. Serum ironsaturation decreased following removal of the spleen. Serum IgM levels fell after splenectomy but IgG and IgA were unchanged. Sources of chronic antigenic stimulation that may have produced the lymphoid hyperplasia included hepatitis antigen, bacterial and other viral antigens, and blood transfusions.The beneficial effect of splenectomy in these patients probably results from restoration of a delicate hematologic balance between hematopoiesis and destruction after removal of a major site of cellular sequestration and destruction and the hyperreactive immunoglobulin-producing lymphoidtissue.