Systemic cyclosporin A (CsA) is currently being used for immunosuppression in solid organ transplantation. Its unique mechanism of action and low myelotoxicity have vastly improved the prognosis for patient survival. A reversible and irreversible nephrotoxicity has complicated its use. CsA works via the inhibition of both lymphokine release and subsequent activation of cytotoxic T cells. The corneal allograft model presents several unique features that make it amenable to local immunosuppressant therapy. Following topical application, CsA corneal levels have been obtained above the experimentally determined levels necessary for local immunosuppression. CsA represents one of a new class of specific, potent immunomodulators, which may improve the prognosis for patients at high risk for allograft rejection.