Phenotypic characterization by monoclonal antibodies of spleen cells obtained from three spleens involved by hairy cell leukemia (about 90% of cells with intracytoplasmic tartrate-resistant acid phosphatase) indicated that the hairy cells are OKT-3-, OKM-1+, and OKIa1+. Neoplastic cells obtained from two lymph nodes involved by B-cell lymphoma were found to be OKT-3-, OKM-1-, and OKIa1+. Functional characterization of the hairy cells present in the spleen indicated that they lack NK activity and do not release Interleukin 1. In fact, spleen hairy cells were not lytic against K-562 tumor cells in a short-term 51Cr-release assay and did not release Interleukin 1 in culture supernatants even after LPS stimulation. In normal individuals, both these cell functions are expressed by subpopulations of OKM-1+ cells.