We asked the recipients of 500 consecutive corneal transplants to return for examination and endothelial photography at two months and at one, three, and five years postoperatively. Thirty-six regrafts and 70 fellow eyes of bilateral cases were excluded, leaving 394 eyes for analysis. We also recorded episodes of graft rejection and failure. In 129 grafts in patients who returned at each postoperative interval and had no rejection episodes, the mean endothelial cell density continued to decrease 7.8% per year from three years to five years after keratoplasty, compared with approximately 0.5% per year in unoperated-on normal corneas. The mean cell loss compared with the preoperative examination was 58.9% five years after keratoplasty. The percentage of hexagonal cells did not return to preoperative levels by five years after keratoplasty, suggesting that the endothelium continued to be unstable. The mean corneal thickness increased significantly with time. The Kaplan-Meier rates of rejection episodes and failure were 19% and 17%, respectively, five years after keratoplasty. Eyes with posterior chamber lens implants lost more endothelial cells by five years after keratoplasty than did eyes with open-looped anterior chamber lens implants. Low endothelial cell densities were statistically significantly associated with increased corneal thickness and with an increased risk of subsequent failure. The central endothelial cells of successful corneal transplants five years after keratoplasty form an unstable monolayer with continued accelerated loss of cells and abnormal cellular morphologic features. This process results in fewer endothelial cells remaining on the central graft with an associated increase in stromal swelling and graft failure.