A 12-week double-blind crossover trial compared fenbufen and indomethacin in 40 patients with rheumatoid arthritis. Fenbufen (600-800 mg/day) was significantly superior to indomethacin (75-100 mg/day) in improving the physical measurements of rheumatoid arthritis activity. Twenty-four patients who demonstrated marked or moderate improvement in the double-blind study participated in a 14-week single-blind study. After one week on placebo, patients received either fenbufen once a day at bedtime, fenbufen twice a day, or indomethacin three times a day for 12 weeks, followed by 2 weeks of placebo. All three treatment groups demonstrated significant improvement. The two fenbufen groups were significantly superior to indomethacin in improving the physical measurements of rheumatoid arthritis activity. No significant differences were found between the two fenbufen treatment groups. Drug-related side-effects reported during both studies were significantly fewer with fenbufen than with indomethacin.