Twelve patients with rheumatic diseases took part in a 6-week double-blind crossover trial comparing 14 days of oral with 14 days of rectal indomethacin treatment, 50 mg 3 X /day, with a 14-day placebo period. The patients had a gastroscopic and a proctoscopic examination after each of the 3 periods. The gastric acid production, serum concentrations and the 24-h urine excretion of indomethacin was measured. Both indomethacin capsules and suppositories caused an equal amount of gastric damage, indicating that the irritative effect of indomethacin on the gastric mucosa is not a local effect, but due to a systemic effect of indomethacin. Although the suppositories caused some mucus discharge no mucosal damage was found by proctoscopy.