The density distribution of endothelial cells was determined, directly and indirectly, by counting cells and cell nuclei in two separate groups of unpaired human corneas. Four areas, measuring 1 square mm each, were counted in the corneal center as well as in the periphery close to Schwalbe's line. In 19 Orcein-stained corneas, the peripheral density of nuclei was 3632/mm2 +/- 592 (SD) as compared with central counts of 2778 mm2 +/- 284 (SD). The other group of 22 corneas, stained supravitally with Alizarin-red revealed a peripheral cell density of 3696/mm2 +/- 721 (SD), in contrast with a central density of 2811/mm2 +/- 425 (SD). There was also an uneven density distribution in the central endothelium. The average difference between the highest and lowest central square millimeter counts in the two groups was 8.0 +/- 7.7% (SD) and 9.0 +/- 3.6% (SD), respectively. The data indicate a nonuniform endothelial cell density distribution in the human cornea that may have clinical implications.