Twenty-one children with chronic thrombocytopenia of obscure etiology, 19 of whom had normal numbers of bone marrow megakaryocytes, were evaluated in order to determine if factors extrinsic to the platelets themselves (presumably antibodies) caused the thrombocytopenia. The rapid destruction of platelets by such antibodies has been demonstrated to cause idiopathic thrombocytopenic purpura (ITP). History, physical examination, and routine laboratory studies were unable to provide an exact diagnosis in these patients. Measurement of platelet survival, using sodium chromate Cr 51 labeled homologous platelets obtained from unrelated donors, permitted a clear separation of these children into two groups. One group (11 patients) had a markedly shortened platelet life span, and was considered to have chronic ITP. The other group (10 patients) had a normal or only slightly reduced platelet life span. Thus, the destruction of platelets by extrinsic factors could be ruled out. Since the diagnosis of chronic ITP was excluded, splenectomy could be avoided in these patients since it is rarely useful in children with nonimmune forms of chronic thrombocytopenia. Homologous platelet survival measurement is a useful diagnostic tool in certain children with chronic thrombocytopenia.