Purpose: To evaluate the joint effects of donor age and cause of death on the endothelial cell density of fresh human corneas. Methods: The corneal endothelial cell density of 946 eyes from 946 donors was analysed. The donors were divided into three age groups: group 1 comprised those aged 50 years and less; group 2 those aged 51-75 years, and group 3 those aged over 75 years. They were also grouped according to the cause of death: group A included those who had died of cancer; group B those who had died of acute myocardial infarction, pulmonary embolism or intracerebral haemorrhage, and group C those who had died as a result of other diseases. Results: There was a statistically significant negative correlation between donor age and mean corneal endothelial cell density, which was 2868 +/- 309 cells/mm(2) in group 1, 2716 +/- 335 cells/mm(2) in group 2, and 2670 +/- 368 cells/mm(2) in group 3. Among the various causes of death, the mean endothelial cell density was 2677 +/- 343 cells/mm(2) in group A, 2741 +/- 367 cells/mm(2) in group B, and 2713 +/- 337 cells/mm(2) in group C. The endothelial cell density was significantly lower in group A than in group B (p = 0.02). When the donors in the oldest age group (group 3) were analysed according to the various causes of death, the difference between group A (2603 +/- 342 cells/mm(2)) and group B (2729 +/- 338 cells/mm(2)) was even more significant (p = 0.0067). Conclusion: Longlasting, severe diseases like cancer, leading to cachexia and catabolism, reduce the number of endothelial cells to a greater degree than diseases that cause a more rapid death. This negative effect of cancer on endothelial cell density is aggravated by the general decline in endothelial cell density with advancing age.