Cyclosporine (cyclosporin A, CsA) is a selective T-cell immunosuppressant that works primarily through inhibition of both antigen presentation and lymphokine production. It has dramatically improved the prognosis for solid organ transplantation. Significant nephrotoxicity has been associated with its systemic use. Topical CsA 2% was used in 11 high-risk corneal transplant patients (8 men; 3 women; average age, 44 years). Ten (91%) of 11 corneas remained clear at an average follow-up of 16 months (range, 6-24 months). All patients had transient epithelial keratitis. Systemic whole blood levels of CsA measured by high-performance liquid chromatography (HPLC) ranged from 14 to 64 ng/ml. All previous reports on the use of topical CsA in high-risk corneal transplant patients have not detected systemic CsA levels.