To obtain longitudinal data to estimate long-term morphometric changes in normal human corneal endothelia. Ten years after an initial study, the authors rephotographed the central corneal endothelium of 52 normal subjects with the same contact specular microscope. The findings for the 10 subjects younger than 18 years of age at the initial examination were considered separately. For the remaining 42 adult subjects, the time between examinations averaged 10.6 +/- 0.2 years (range, 10.1 to 11 years). At the recent examination, these subjects' ages averaged 59.5 +/- 16.8 years (range, 30 to 84 years). Outlines of 100 cells for each cornea were digitized. For the 42 adult subjects, the mean endothelial cell density decreased during the 10.6-year interval from 2715 +/- 301 cells/mm2 to 2539 +/- 284 cells/mm2 (P < 0.001). The calculated exponential cell loss rate over this interval was 0.6% +/- 0.5% per year. There was no statistically significant correlation between cell loss rate and age. During the 10.6-year interval, the coefficient of variation of cell area increased from 0.26 +/- 0.05 to 0.29 +/- 0.06 (P < 0.001), and the percentage of hexagonal cells decreased from 67% +/- 8% to 64% +/- 6% (P = 0.003). For the 10 subjects 5 to 15 years of age at the initial examination, the exponential cell loss rate was 1.1% +/- 0.8% per year. Human central endothelial cell density decreases at an average rate of approximately 0.6% per year in normal corneas throughout adult life, with gradual increases in polymegethism and pleomorphism.