Evidence is presented that some endogenous Langerhans cells (LCs) may persist indefinitely in skin grafts. This evidence is based on the observation that although 2 weeks after grafting F1 hybrid mice and rats with genetically compatible skin, most of the LCs in the grafts were replaced with those of the host, some LCs of graft origin persisted for as long as the grafts were followed (154 days in mice and 249 days in rats). It has also been demonstrated that the spleen may be as good a source of LCs as the marrow. Thus, 6 weeks after lethally irradiated mice were restored with F1 hybrid spleen cells, most of the LCs in the epidermis of their pinnae were of donor origin. LCs of donor origin also were found in the epidermis of the pinnae of animals that had been inoculated at birth with spleen and lymph node cells (mice) or bone marrow cells (rats). Hence the occurrence of these cells provides another means of confirming that tolerance (chimerism) has been induced.