Phenotypic and functional alteration of murine CD4+ T cells after antigenic stimulation was studied using two anti-T cell mAbs recently described that define four distinct T cell subsets. Activation of T cells resulted in the permanent loss of 3G11 expression. However, two phenotypically distinct memory T cell populations were established depending on the system used; whereas those for anti-KLH antibody response were enriched in the fraction expression 6C10 (Fr. III), memory T cells for the allogeneic MLR lacked such expression (Fr. IV). Furthermore, successive stimulation with antigen in vitro resulted in secretion of IL-4 without detectable IL-2. This alteration of phenotype and interleukin secretion was also demonstrable when starting with 3G11+6C10- cells (Fr. I), the fraction that secretes IL-2 exclusively upon activation.