We tested the ability of 15-deoxyspergualin (DSG), a new immunosuppressant, to inhibit corneal allograft rejection in the rat penetrating keratoplasty model. Fifty-six inbred Lewis rats were recipients of orthotopic corneal allografts from Brown Norway rats. Allogeneic groups received daily intramuscular injections of DSG 2, 3, 4, or 10 mg/ kg/day. The animals treated with 2 mg/kg/day had four out of 10 grafts rejected; in the 3 mg/kg/day group none of the six grafts rejected; whereas in the 4 mg/kg/day group one out of 15 grafts rejected. The animals treated with 10 mg/kg/day became emaciated and died during the second and third postoperative weeks with relatively clear grafts. All corneas rejected following discontinuation of the drug. We conclude that the systemic administration of DSG at 3 or 4 mg/kg/day results in effective suppression of corneal allograft rejection in the rat penetrating keratoplasty model.