An animal model for corneal graft rejection is described in which corneal neovascularization is induced prior to keratoplasty. This model closely resembles high-risk human corneal grafting, and relies on rejection being initiated solely by the transplanted corneal tissue. All eleven allografts performed using this model rejected; median time to rejection was 17 days. Two treatment regimens were assessed using this rejection model. Topical cyclosporine produced a significant improvement in graft survival (P = 0.0025). When systemic cyclosporine was administered there was a highly significant improvement in graft survival (P = 0.0001).