A clinicopathologic analysis of 16 cases of multicentric angiofollicular lymph node hyperplasia (MAFH) was performed. Histologically, the disease was characterized by recognizable lymph node architecture that was at least partially intact, by paracortical hyperplasia with prominent vascular proliferation, and by numerous evenly distributed, apparently benign germinal centers of various types, usually including some typical hyaline-vascular centers. At the onset of the disease, 12 patients had the plasma cell (PC) type of MAFH, three patients had the hyaline-vascular (HV) type, and one patient presented with PC and HV types at separate sites. Transitions between the PC and HV types were observed in two cases. Immunologic studies demonstrated polyclonal populations of plasma cells in the lymph nodes of all patients and the absence of suppressor T lymphocytes in the one patient tested. Clinically, the patients had constitutional symptoms, multicentric lymphadenopathy, hepatosplenomegaly in many cases, and abnormal laboratory findings, including anemia, polyclonal hypergammaglobulinemia, and bone marrow plasmacytosis. The 16 patients were placed in four different clinical groups based on presentation and course: stable disease, chronic relapsing disease, aggressive disease, and development of malignant lymphoma. Ten of the 16 patients died (median survival, 26 months; range, eight to 170 months). Multicentric angiofollicular lymph node hyperplasia appears to be a variant of classic angiofollicular lymph node hyperplasia (Castleman's disease) and is associated with significant morbidity and mortality.