Biologic, functional and chemical characterization of cell surface structures of normal lymphoid and malignant cells are under investigation. Antigen (HLA) controlled by the major histocompatibility complex (MHC) have been assessed in diseased populations and at risk families. Results indicate that several interacting genes and gene orientation predispose to disease states and immune response. Immunoprecipitation analysis of antigens controlled by the MHC DR gene region suggest at least 3 gene products. Antisera detecting some of these antigens inhibit antigen stimulation and Ig synthesis when these sera are reacted with monocytes and acute lymphocyte leukemia cells. This inhibition has been determined to be due to suppressor T cell activation. Three monoclonal antibodies 3A1, 4F2, and 5E9 have been characterized for antigen specificity molecular weight of antigen detected and normal cellular distribution of antigens. These monoclonal antibodies have been used to determine phenotypes of malignant cells of lymphoid origin. Cells from patients with Sezary syndrome are 3A1- 4F2+, a phenotype not found on normal cells. Acute lymphocytic and myeloid leukemia cells exhibit a wide variation in antigen expression suggesting dedifferentiation of cells undergoing malignant transformation.