To determine the maturation arrest of the neoplastic cells of hairy- cell leukemia (HCL) and the spectrum of the surface markers on these cells, a series of 51 patients with this disease was studied. The cells of all but two of the patients showed monoclonal surface Ig with respect to light chains. In about one-third of the cases, only gamma heavy chain determinants were present on the cells; the majority carried multiple heavy chain determinants as documented by the application of different fluorochromes. Two patients each showed two different clones of cells, both of the same light chain type. In one of these two patients, two paraproteins were present in the serum. Intracytoplasmic Ig was found in only 4 of 39 cases, in all instances being IgM. All cases studied concerned cells with FclgG receptors; however, the density of this receptor varied. FcIgM receptors also showed a spectrum of density, with some cases showing very few FcIgM- positive cells. Receptors C3 were not observed on the hairy cells. Serum immunoglobulin levels were normal or increased. Paraproteins were found in the sera of 4 of 38 patients. These data suggest that HCL is a neoplasm of B lymphocytes. The neoplastic cells are probably arrested at a more mature stage than the cells of chronic lymphocytic leukemia. The multiple isotypes on the cells indicate a block at the “switch” phase from the small micro-carrying lymphocyte to the larger Ig- producing lymphocyte or plasma cell.