Hairy-cell leukemia is a neoplastic disorder of lymphoreticular cells which has been reported under a variety of names, including “leukemic reticuloendotheliosis,” “chronic reticulolymphocytic leukemia, ” and “ reticulumcell leukemia. ” Clinically, it is characterized by insidious onset, splenomegaly, little or no lymph node involvement, and the presence of characteristic hairy cells in the blood and bone marrow. In this study we present the clinical and morphologic findings of five cases of hairy-cell leukemia, and we describe the ultrastructure of hairy cells from one case. Only one patient was frankly leukemic, and in all but one case, the bone marrow aspirates contained few marrow particles which were mixed with blood. In four cases, a bone marrow biopsy was necessary in order to obtain an adequate specimen. The histologic picture of the marrow biopsy appears to be distinctive and diagnostic. Enzyme cytochemical methods for esterases gave reactions similar to those seen in monocytes and reticulum cells; however, morphologically by light and electron microscopy, the cells were different from lymphocytes, monocytes, and reticulum cells. Hairy-cell leukemia should be differentiated from other types of leukemia and lymphoma. The exact nature and origin of the hairy cell remain unknown.