Diflunisal (500 mg orally, twice daily) and naproxen (375 mg orally, twice daily) were compared for efficacy and tolerability in a 12-week open-label study in 33 patients with active rheumatoid arthritis (RA). Both drugs resulted in marked reduction in the number of swollen, tender, and painful joints and comparable improvement in patients' assessment of disease activity and pain. There were no significant differences between the two medications in the measured indices of disease activity. No adverse experiences were reported by patients in either treatment group. The results indicate that both diflunisal and naproxen were equally effective and that both agents are generally well tolerated in this group of patients with RA.