Corneal allografts can elicit a host immune response that results in their destruction as functional tissues. Just as with other types of tissue allografts, effective, safe methods are needed to prevent corneal allograft rejection in patients undergoing penetrating keratoplasty. In this study, cyclosporin A, a compound of fungal origin, was tested for its capacity to suppress corneal allograft rejection in rabbits. Corneal allografts were exchanged between pairs of randomly bred albino rabbits. Some animals received retrobulbar injections and others received similar injections of the drug vehicle only. Cyclosporin A significantly prolonged corneal allograft survival. All the allografts in untreated eyes were rejected within 40 days; four (45%) of the nine allografts in treated eyes survived more than 70 days. Cyclosporin A alone was less effective in suppressing allograft rejection in heavily vascularized, inflamed graft sites. No adverse side effects were seen when it was injected locally into the rabbit eye. We conclude that in the acute graft model in this study, cyclosporin A is a safe, potent immunosuppressive agent.