Functionally disparate subpopulations of T lymphocytes that respond to alloantigens, primarily as studied in vitro in the mixed leukocyte culture and cell mediated lympholysis assays, have been separated most usefully by cell surface markers that can be identified with antiserums. Based on the data available to date there are at least two, and perhaps three, T lymphocyte subpopulations responsive to alloantigens in vitro, which include helper, cytotoxic, and perhaps suppressor T lymphocytes. Reviewed in this paper are data pertaining to the question of whether two types of cytotoxic T lymphocytes exist and whether true memory cytotoxic T lymphocytes are generated following in vitro or in vivo priming. Further, two systems are discussed that served as differentiation markers on lymphocytes: the Ly antigens and a family of large cell surface membrane proteins (LMPs).