Antigenic stimulation of CD4/CD8 double positive (DP) thymocytes results in programmed cell death, while the identical stimulation of mature T cells results in proliferation and lymphokine secretion. Using thymocytes from transgenic mice expressing pigeon cytochrome c-specific T cell receptors, we previously demonstrated that major histocompatibility complex class II-transfected L cells were capable of presenting peptide antigen and inducing programmed cell death in DP thymocytes, as well as proliferation and lymphokine secretion in mature CD4 single positive (SP) T cells. We therefore were interested in utilizing this system to compare antigen-induced signal transduction events in DP thymocytes and mature SP T cells. In this report, we demonstrate that significant distinctions between thymocytes and mature T cells are seen upon examination of antigen sensitivity and the phosphatidylinositol signaling cascade.