Two major functionally distinct T cell subsets in man have been defined with heteroantiserums and monoclonal antibodies directed against stable cell surface antigens that appear during thymic ontogeny. A monoclonal antibody to T4 antigen (anti-T4) is reactive with the peripheral inducer T cell population while a monoclonal antibody to T5 antigen (anti-T5) is reactive with the cytotoxic and suppressor population. Immunoprecipitation and electrophoresis on sodium dodecyl sulfate polyacrylamide gel were used to show that on human thymocytes or peripheral T cells the T4 antigen is a single 62,000-dalton glycoprotein while the T5 antigen is a complex of two glycoproteins, one being 30,000 daltons and the other 32,000 daltons. Similar glycoproteins have been isolated with antibodies to murine Lyt 1 and Lyt 2,3 antigens. Both the antigens defining the phenotypes of inducer and suppressor populations in man and mouse are structurally homologous.