Neovascularization of the cornea occurs in numerous pathologic states causing decreased visual acuity and blindness and is a major complication of corneal allotransplantation. The purpose of this study was to investigate the effect of topical and systemic cyclosporin A (CsA) on corneal angiogenesis induced by xenotransplantation or by chemical cauterization. The subcutaneous disc angiogenesis system (DAS) also was used to study the effects of CsA on angiogenesis in a nonocular site.Corneal angiogenesis was provoked by either xenotransplantation or chemical cautery. Rats from experiments using both of these models were subdivided into four treatment groups. Topical treatment was administered by using 4% CsA eye drops or vehicle (castor oil) four times daily for 10 days. Systemic therapy consisted of daily (5 mg/kg per day) subcutaneous injections of CsA or vehicle. In the DAS experiments, rats received CsA or vehicle systemically or intradisc. The amount of neovascularization was quantitated by digital image analysis in corneal flat preparations and sections of discs.Rats that received xenografts or cautery manifested less corneal neovascularization than did control animals after topical of subcutaneous CsA treatment. CsA also enhanced the survival of corneal xenografts. A difference between CsA and vehicle-treated animals in the DAS experiments was not detected.CsA effectively retards the growth of new vessels in the cornea after xenotransplantation or chemical cauterization and prolongs xenograft survival. However, CsA does not suppress angiogenesis in all systems, because it was ineffective in blocking vessel growth in the subcutaneous DAS.