A scanning electron microscopy (SEM) study was performed on the gastric and duodenal mucosa of 14 patients treated with Aspirin or Piroxicam. Six patients with normal mucosal morphology were treated with either 1.5 g/day of Aspirin (3 patients) or 20 mg/day or Piroxicam (3 patients) for one month. In addition, 8 rheumatic patients were treated with a similar dose of Aspirin (4 patients) or Piroxicam (4 patients) for at least 4 months. SEM was used to evaluate the following parameters: mucosal structure, cellular exfoliation and anisocytosis, alteration of the microvilli (blebs). The mucosa showed various aspects of alterations ranging from minimal changes (microvillar alteration) to a completely subverted structure both in the stomach and in the duodenum. Mucosal changes, both on the edge of the macroscopic lesions and at a distance from these, were visible with SEM even when endoscopy was normal. Piroxicam appeared slightly less damaging than Aspirin, and no difference was observed between short-term and long-term treated patients, either with Aspirin or with Piroxicam.