Fourteen of 172 uremic chronically hemodialyzed patients developed pancytopenia and significant increases in transfusion requirements which were corrected by splenectomy. Histologic examination of the spleens showed a striking degree of lymphoid hyperplasia not seen in spleens from two control groups. Bone marrows in the study group were hypocellular before splenectomy and did not differ in cellularity after surgery, or when compared with a control group. There was a significant drop in serum IgM levels after splenectomy. Chronic non-negated antigenic stimulation manifested by the high incidence of chronic, persistently HAA(+) hepatitis is probably responsible for the heightened splenic lymphoid reactivity. These patients are marginally able to maintain circulating blood levels, and we postulate that a slightly increased degree of splenic sequestration resulting from the heightened abnormal lymphoid activity produces a hypersplenic syndrome by altering the delicate hematologic balance. Splenectomy decreases peripheral blood cell destruction not only by removing a site of relatively normal sequestration, but also by removing a major site of immunoglobulin production.