AIMS--To describe the ultrastructural changes that occur in human antral mucosa following direct application of aspirin in volunteers without Helicobacter pylori infection. METHODS--Ten healthy male volunteers without H pylori infection underwent three consecutive endoscopies (at zero, one and five hours). At the first endoscopy, two biopsy specimens were obtained (one for histology and the other for electron microscopy (EM)). At subsequent endoscopies, a single biopsy specimen was obtained for EM. A 50 ml solution of aspirin (concentration 3 mg/ml) was applied to the antral mucosa at the first endoscopy in five subjects; the other five subjects received 50 ml distilled water (placebo). RESULTS--The ultrastructural appearance of the first biopsy specimen in all subjects and subsequent biopsy specimens in the placebo treated subjects was normal. The aspirin treated group had evidence of intercellular oedema, widening of capillary fenestrae, rupturing of apical membranes, and dilatation of endoplasmic reticulum and mitochondria after one hour; these changes were more marked at five hours. Tight junctions were maintained. CONCLUSION--This is the first study to describe the early ultrastructural changes in antral mucosa induced by aspirin in subjects without H pylori infection.