The purpose of this study was to determine the effect of splenic irradiation on the hematologic manifestations of hypersplenism: hemolytic anemia, granulocytopenia, and thrombocytopenia. Eight patients with hypersplenism secondary to various diseases had their spleens irradiated with doses of between 700 and 2,000 r in a period of 8 to 17 days. Although most of the patients had some clinical improvement, related particularly to the reduction in spleen size, the hypersplenic manifestations showed little response to the treatment. Only 1 patient had a lasting remission of hemolytic anemia, and even this was not clearly attributable to splenic irradiation. Splenectomy was effective in controlling hypersplenism, and, when feasible, is the treatment of choice for this condition.