PURPOSE: We evaluated the therapeutic effect of 0.5% topical cyclosporine on human corneal allograft rejection. METHODS: Sixteen patients (16 eyes) with corneal allograft rejection, refractory to the conventional treatments, were recruited and treated with 0.5% cyclosporine eyedrops in this study. RESULTS: Of 16 eyes with corneal graft rejection after penetrating keratoplasty treated with 0.5% cyclosporine eyedrops, nine eyes were completely cured, six eyes improved markedly, and treatment was ineffective in one eye. A follow up of 12 to 24 months (three eyes for 12 months, five eyes for 18 months, and eight eyes for 24 months) disclosed that rejection recurred in three of the nine cured eyes-two eyes after suspension of cyclosporine and one eye after removal of the sutures. The recurrence of rejection resolved by resumption of the cyclosporine eyedrops. CONCLUSIONS: This study demonstrated that treatment of corneal graft rejection with 0.5% topical cyclosporine yielded good results in eyes with satisfactory preoperative corneal transplantation beds and beneficial effects in eyes with poor preoperative corneal transplantation beds.