The goal is to analyze human lymphoma and lymphocytic leukemias with hybridoma antibodies defining T-cell subsets in order to develop a comprehensive classification of human lymphomas based on the functional characteristics of the malignant cell and to provide an improved basis for treatment selection and prognostication. During the past year suspensions prepared from 12 specimens of nonneoplastic thymus (six normal and six from patients with myasthenia gravis) and from 17 thymomas were investigated with a panel of monoclonal antibodies. The great preponderance of thymocytes from the 12 nonneoplastic specimens and from 12 of 13 thymomas (two of three predominantly lymphocytic tumors and 11 of 12 mixed tumors) displayed the surface phenotype of cortical or common thymocytes. These cells formed rosettes with unsensitized sheep erythrocytes (E-rosettes) at both 4 and 37~C, and reacted with the following monoclonal antibodies: OKT1 (thymic and peripheral T cells), OKT6 (common thymocytes), OKT10 (replicating lymphoid cells), OKT11 (sheep cell receptor), and both OKT4 (inducer-helper T cells) and OKT8 (cytotoxic-suppressor T cells). Few B cells (lymphocytes with either immunoglobulin or Ia-like antigen on the cell surface) and few cells with receptors for transferrin and interleukin-2 were detected. Thymocytes from three of the four remaining thymomas (two predominantly epithelial tumors and one mixed tumor) displayed surface marker characteristics of medullary thymocytes or peripheral T cells; i.e., they were reactive with OKT1, OKT3 (peripheral T cells), OKT11, either OKT4 or OKT8, and were also E-rosette positive only at 4~C and TdT negative. Thymocytes from the final tumor, a lymphocytic thymoma, exhibited an intermediate phenotype. Thus, almost all mixed (11 or 12) and lymphocytic (two of three) thymomas were composed predominantly of cortical thymocytes, while the medullary cell was the rule in the two tumors that were predominantly epithelial. (2)