The prime aim of this study was to assess whether the autonomous primary mixed lymphocyte culture response of Lyt-2+ T cells towards class I major histocompatibility complex (MHC) antigens reflects in terms of interleukin 2 (IL2) production and cytotoxicity the activation of multifunctional Lyt-2+ T cells, or the activation of functionally distinct T cell subsets. The results demonstrate that highly purified Lyt-2+ T cells proliferate in response to class I MHC antigens, as opposed to L3T4+ T cells which react towards class II MHC antigens. In both responder cell types proliferative responses are associated with IL2 secretion, while only Lyt-2+ T cells develop measurable cytotoxic effector cells. The precursor frequency of IL2-producing helper cells in MHC class I-reactive Lyt-2+ T cells equals that in MHC class II-reactive L3T4+ T cells (f = 1/500-1/1000). In clonal segregation analysis greater than 90% of Lyt-2+ colonies secreting IL2 do not develop cytotoxic activity, while greater than 90% of Lyt-2+ cytotoxic T cells fail to produce detectable IL2. A minority of less than 10% of Lyt-2+ T cells appears to be bifunctional. As such the results point out the existence of functionally committed T cells within class I MHC-reactive Lyt-2+ T cells able to produce either IL2 or to develop into cytotoxic effector cells.