We have studied ten patients with a lymphoproliferative disorder characterized by massive splenomegaly; minimal lymphadenopathy; varying degrees of blood cytopenias; circulating atypical lymphoid cells frequently with "hairy" cytoplasm; monoclonal serum paraprotein; and tartrate-resistant acid phosphatase reactivity in the tumor cells of five patients tested. Although the clinical and laboratory features in most cases prompted a clinical diagnosis of "hairy cell leukemia" (HCL), histologic, ultrastructural and immunohistologic studies of multiple organs revealed distinctive features recognizably different from leukemic reticuloendotheliosis (LRE). Because this B lymphocyte proliferation may be mistaken for LRE in cases where careful histologic study is not performed, it may be responsible in part for the conflicting data in attempts to characterize the cell of origin of the latter disease. Clinical and experimental data in HCL must be questioned if they do not include histopathologic confirmation of the diagnosis.