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Hemorrhagic thrombocythemia is a relatively well-defined myeloproliferative disease in which the major abnormality is the excessive production of megakaryocytes and platelets. In its natural evolution acute and chronic bleeding from the gastrointestinal tract, thromboembolic phenomena, gastric and esophageal varices, and infarction atrophy of the spleen are the important clinical features. Disastrous complications may follow splenectomy. Removal of the spleen by surgery, or infarction and atrophy allows masses of platelets to circulate which produce thrombi or emboli in small vessels and ultimately hemorrhage. Effective treatment requires the suppression of megakaryocyte growth and thrombopoiesis. In four patients who developed severe postsplenectomy hemorrhagic thrombocythemia, melphalan (L-phenylalanine mustard) therapy effectively controlled the abnormal thrombocytosis and clinical evidence of disease.