Castleman's disease (also called giant lymph node hyperplasia or angiofollicular lymph node hyperplasia) is a clinicopathological entity of unknown etiology. Two histologic patterns of lymph nodes are classically recognized: the hyaline-vascular and plasma-cell variants. Recently, multicentric Castleman's disease has emerged as a separate clinical entity manifested primarily by generalized lymphadenopathy and systemic manifestations, such as thrombocytopenia, hemolytic anemia, hepatosplenomegaly, altered liver function tests, central nervous system alterations, and autoimmune manifestations. A number of renal alterations have been described in association with the two pathological variants of Castleman's disease, but thrombotic microangiopathy has been previously reported only once in a patient with Castleman's disease. No renal biopsy was performed in that patient, although there was evidence of renal dysfunction. We report two cases of biopsy-proven renal thrombotic microangiopathy associated with multicentric Castleman's disease. In addition to having lymph node pathology characteristic of Castleman's disease, both patients presented with generalized lymphadenopathy and systemic manifestations, including acute renal failure, hypergammaglobulinemia, anemia, thrombocytopenia, and hypoalbuminemia. Autoantibodies were present in both patients, including antiphospholipid antibodies in one patient. The renal biopsies, examined by light, immunofluorescence, and electron microscopy, were diagnostic for renal thrombotic microangiopathy. The simultaneous development of two rather uncommon syndromes, multicentric Castleman's disease and renal thrombotic microangiopathy, suggests a possible link between Castleman's disease and renal thrombotic microangiopathy. Furthermore, we propose that the production of autoantibodies, in particular antiphospholipid antibodies, may lead to the development of thrombotic microangiopathy in some patients with multicentric Castleman's disease.