The purpose of this study was to characterize age-associated changes in the corneal endothelium and Descemet's membrane (DM) in C57BL/6 mice, an inbred strain commonly used as a genetic disease model. Corneas from mice aged 2 weeks to 24 months were studied. Light microscopy was used to assess central endothelial cell density, area, and morphology. Transmission electron microscopy was used to assess thickness and ultrastructural features of DM. Central corneal endothelial cell density showed a rapid decline from 5,232+/-892 cells/mm(2) (mean+/-S.D.) at 2 weeks to 2,532+/-112 cells/mm(2) at 16 weeks of age. Thereafter, cell density declined more slowly, reaching 2,004+/-134 cells/mm(2) at 24 months of age. DM thickness showed an approximately linear increase from 1.12+/-0.22 microm (mean+/-S.D.) at 2 weeks to 4.19+/-1.17 microm at 24 months of age. DM in 2 and 6 week age groups was composed entirely of material with an electron dense, periodic banding pattern. Sixteen week, 12 month, and 24 month age groups exhibited an additional, progressively thicker, homogeneous layer lacking periodic banding. The observed age-dependent thickening of DM was predominantly due to accumulation of the posterior, non-banded layer. In C57BL/6 mice, central endothelial cell density declines with age and DM progressively thickens due to accumulation of a posterior, non-banded portion. These age-associated changes are strikingly similar to observations in humans and thus further support the potential usefulness of the mouse model for studying disorders of the corneal endothelium and Descemet's membrane.