BN male trunk skin grafts, the Langerhans cells (LC) of which have been replaced with major histocompatibility complex (MHC)-incompatible Lewis female cells, survive longer on BN female rats than BN male trunk skin grafts bearing BN female LC. Evidence is presented that the privilege afforded these grafts is a consequence of MHC restriction. Thus, supplanting the native LC population of BN male trunk skin grafts with MHC-compatible Lewis.1N female cells has no affect on their survival on BN female rats. Evidence is also presented that H-Y-incompatible isografts deficient in MHC-compatible LC induce tolerance of H-Y.