The morphology, immunologic and functional properties of peripheral blood and bone marrow cells or cultured cells from 2 patients with clinically aggressive non-T, non-B lymphoma/leukemia are described. The leukemic cells possessed medium to large granules in the cytoplasm, antigens against CD38, CD2, CD25, OKIa1, CD16, TA-1, CD9, CD24 and NKH-1 (N901) monoclonal antibodies on their cell surface, and also showed a high natural killer (NK) activity. Phenotypically, the cells in these disorders were quite different from T gamma leukemia cells bearing Fc receptor or the traditionally reported NK leukemia cells possessing HNK-1 (Leu 7) antigens on their surface. In addition, these leukemias/lymphomas belonged to neither T- nor B-cell lineage, proved by studying clonal gene rearrangement for the T beta and T gamma receptor, and immunoglobulin. Hence, a quite interesting and important point, as suggested by our data, is that all our cases expressed an antigen for NKH-1 (N901), which is detectable on all NK cell surfaces and they lacked the antigen for Leu 7 (HNK-1), which is usually detected on the surface of leukemic NK cells. These facts indicate that we are dealing with a leukemic NK cell subset which is quite different from cells of all other reported cases of NK cell leukemias. We therefore concluded that such disorders with an aggressive clinical nature and a poor prognosis as in our cases belong to a new clinical entity originating from a portion of the NK cell subset.(ABSTRACT TRUNCATED AT 250 WORDS)