Whether a seven days course of anti-${alpha}{eta}$-T cell receptor-antibody (${alpha}{eta}$-TCRmAb) combined with FK506 therapy promotes survival of limb allografts in fully MHC-mismatched combination (Brown Norway $ ightarrow$ Lewis) was examined. Eight animals received 250 ${mu}g$/kg/day of ${alpha}{eta}$-TCRmAb for 7 days and 2 mg/kg/day of FK506 postoperatively (Combination therapy group). Eight animals had FK506 only (Mono-therapy group) and five animals did not have treatment (Control group). Clinical signs of early rejection with edema or erythema in the skin occurred at an average of 8.6${pm}$1.5 days postoperatively in Control group and 59.0${pm}$8.3 days in Mono-therapy group, both of which proceeded to irreversible rejection with necrosis of the epidermis and finally mummification. In Combination therapy group, all animals showed evidence of early rejection at an average of 56.8${pm}$12.6 days postoperatively, however, in 4 of 8 limbs, early rejection resolved without any treatment and limbs survived >1 year. At 9 months postoperatively, donor skin grafts were accepted and third-party skin grafts were rejected by all four survivors, demonstrating donor-specific tolerance. Little or no detectable chimerism was observed in any of the 4 surviving animals at one-year postoperatively. Combination therapy of ${alpha}{eta}$-TCRmAb and FK506 resulted in long-term survival in fully MHC-mismatched limb transplants.