We examined histologic and ultrastructural changes in the gastric mucosa of aging rats. Standardized gastric specimens from Sprague-Dawley rats 3 months of age (young) and 24 months of age (old) were evaluated by qualitative and quantitative histology and transmission electron microscopy. Old rats had the following histologic changes: (1) partial atrophy of the gastric glands and their replacement with hyalinlike connective tissue; (2) cystic dilatation of the gastric glands at the bases with occasional squamous cell metaplasia; and (3) extensive perivascular depositions of PAS-positive material, negative for amyloid. The total mucosal thickness was 484 +/- 100 microns in young rats vs 1122 +/- 240 microns in old rats (P less than 0.01). Electron microscopy demonstrated degenerative changes in parietal and chief cells, hyperplasia of surface and foveolar mucous cells, and prominent accumulation of disorganized collagen fibrils in perivascular connective tissue. This study indicates that the gastric mucosa of aging rats that have not been exposed to damaging agents does show definite histologic and ultrastructural changes.