Over the past several years, a number of major advances have been made in our understanding of the phenotypic and functional heterogeneity of human T lymphocytes. Most of these advances have resulted from: 1. the availability of monoclonal antibodies directed to T cell surface antigens; 2. the development of sensitive microassays to measure lymphocyte function in vitro; 3. the refining of T cell cloning technology. The most relevant studies in delineating how human T cell functions have been based on the analysis of T cell clones with specific cytolytic activity. These studies allowed the recent molecular definition of structures serving as specific antigen receptor on T cells as well as the understanding of the role of accessory molecules involved in specific receptor activity such as T3, T8 and T4 antigens. The development of microculture conditions allowing clonal proliferation of all human T lymphocytes, whether resting or activated, has provided a major tool for the precise definition of the frequency and subset distribution of T cells with different functional capabilities. Studies along this line have shown that precursors of cytolytic T lymphocytes (CTL-P) represent about one third of peripheral blood human T lymphocytes; in addition, all T8+ were CTL-P, whereas CTL-P were relatively rare among normal T4+ lymphocytes. As much as 20% cytolytic T lymphocytes were found to be capable to release interleukin-2 and B cell growth factor, thus indicating that cytolytic and helper function may be associated at the single cell level.