This endoscopic study was performed to compare the gastroduodenal endoscopic findings after short-term treatment with plain and enteric-coated piroxicam tablets. Sixteen healthy male volunteers (mean age, 22 years; range, 19-27 years) were included in a double-blind, randomized study in which 20 mg piroxicam was given once daily for 2 weeks as plain tablets or enteric-coated tablets in a crossover fashion. The washout period was 5 weeks, and endoscopy was performed before each treatment period to ensure base-line conditions. Endoscopic evaluation of the stomach and duodenum was performed, with separate registration of the duodenum distally to the duodenal bulb. Visual analogue scales of 150 mm were used for grading the mucosal lesions, with separate registration of mucosal injection and erosive and haemorrhagic lesions. A 5-point scale (Lanza scale) was also used, to compare the two scoring systems. A significantly lower lesion score was found with the enteric-coated formulation for all endoscopic variables in both scoring regions. The sum of visual analogue scale scores in the stomach/duodenal bulb after treatment was 121 mm and 74 mm, respectively (p < 0.01), and in the middle and distal duodenum the corresponding figures were 54 mm and 23 mm (p < 0.01). The fixed-point scoring gave identical conclusions, as did the separate scoring by a different investigator evaluating the same endoscopies. Subjective symptoms were similar for the two formulations, and no carryover effects were detected. We conclude that enteric coating of piroxicam tablets may offer a means of protecting the gastroduodenal mucosa in short-term treatment of healthy subjects.