Starting with single cases in 1985, we have routinely applied systemic cyclosporin A since 1987 in high-risk keratoplasty patients for a period of up to 37 months postoperatively. In all, 69 eyes undergoing 74 perforating keratoplasties have thus far been treated. A considerable percentage of them initially suffered from chemical burns or from endogenous eczema associated with chronic atopic inflammation. All patients were followed closely and their courses were reevaluated retrospectively. Our current conclusions are that (1) immune reactions are efficiently inhibited with constantly effective blood levels of cyclosporin A, which has enormously increased the rate of keratoplasty successful in these patients; (2) if drug blood levels fall too low due to noncompliance of the patient or to metabolic disturbances, immune reactions may occur, especially during the early postoperative months; (3) serious chronic surface problems, which are especially associated with chemical burns, atopic inflammation, and other chronic kerato-conjunctival diseases, are partly ameliorated but not completely eliminated (surface disorders are presently ranked as the number one cause of transplant failure, whereas immune reactions can be effectively suppressed by cyclosporin A); and (4) close medical follow-up has revealed no serious systemic complication of cyclosporin A prophylaxis over periods of up to 37 months. The present study was not conducted in a prospective, double-blind, controlled fashion.