One hundred eighty-five consecutive corneal transplants were performed in recipients selected on the basis of the best available HLA-A,B and DR match. Endothelial rejection-free transplant survival in this group was compared to a retrospective historical control group of 199 consecutive transplants performed in recipients selected on the basis of age and longest wait criteria. The two groups were comparable with regards to primary diagnosis, preoperative corneal vascularization, donor and recipient age, and operative techniques. Thirty-eight transplants in the study group and 28 transplants in the control group were at high risk for endothelial transplant rejection. At 12 months, the estimated rejection-free survival (Kaplan-Meier method) of the high-risk study group transplants was 87% compared to 74% for the high-risk historical control group and transplants. This difference did not reach the significant level of 0.05 with the log-rank test. The 12-month estimated rejection-free survival of low-risk study group and historical control group transplants were similar. In the study group, the 12-month estimated rejection-free survival of well-matched transplants was 95% compared to 83% for poorly matched transplants (log rank, P less than 0.02). These findings suggest that a relationship exists between HLA-A,B and DR compatibility of donor and recipient and the corneal rejection-free transplant survival.