Cytotoxic T lymphocytes (CTL) play an important role in the rejection of allogeneic cells and organs. CTL secrete granzymes and perforin as cytotoxic effector molecules. The mannose 6-phosphate receptor (Mpr)300 has been reported to function as receptor for granzyme B on target cells and to be essential for the rejection of allogeneic cells in vivo. Using mouse embryonal fibroblasts from Mpr300 and Mpr46 knockout mice, we show that both Mpr 300 and Mpr46 are dispensable on target cells for lysis and apoptosis mediated by alloreactive CTL in vitro and for allorejection in vivo. In agreement with a postulated function of Mpr300 as a tumor suppressor gene, deficiency of Mpr300 appears to promote cellular proliferation and tumorigenicity but not resistance to allorejection.