From CBA mice immunized with mouse L cells that express a cloned gene for the human transferrin receptor (hTR) we have isolated cytolytic T cells (CTL). The CTL were Lyt-2+/L3T4- and lysed L cell transfectant clones that expressed the hTR gene but not control untransfected L cells or transfectants selected for the expression of an unrelated human cell surface antigen, 4F2. Lysis of independent hTR transfectant clones correlated with the relative level of receptor expression. The availability of CTL directed against a non-major histocompatibility complex-controlled cellular protein-like hTR may provide an interesting model system for studying antigen processing and recognition.