This study shows that alloantigen presentation via the anterior chamber (AC) of the eye coupled with a single high dose cyclophosphamide (CP) (100 mg/kg) treatment effectively suppresses the skin graft rejection reaction of the recipient. Lewis (Le) rats bearing allogeneic Brown Norway (BN) skin implants in the AC of the eye demonstrate a modest increase in the survival time of orthotopic BN skin grafts. A slight prolongation of the survival of orthotopic BN skin grafts was also demonstrated in nonimplant or syngeneic implant-bearing Le recipients which received a single injection of a large dose of CP. Augmentation of suppression was evident in rats which were treated with a single dose of 75 mg/kg CP but not 25 mg/kg. The augmentation of suppression was evident when CP treatment and skin grafting of the recipient occurred on either 0, 7, or 14 days postimplantation. Recipient splenectomy did not interfere with the augmentation of suppression.