The efficacy and safety of benoxaprofen and sulindac were compared in patients with rheumatoid arthritis and osteoarthritis. A double-blind, crossover protocol was used with three placebo periods. Fixed doses--600 mg of benoxaprofen once a day and 200 mg of sulindac twice a day--were used. Rheumatoid arthritis patients showed significant improvement in most measurements with both drugs, but overall results favored benoxaprofen, particularly in erythrocyte sedimentation rate and physician's global assessment. Results were fairly equal in osteoarthritis patients. Propoxyphene consumption was less during the benoxaprofen therapy period for both groups of patients. Adverse reactions in combined rheumatoid arthritis and osteoarthritis patients generally were mild to moderate. Gastrointestinal complaints were more common with sulindac, while skin reactions were more common with benoxaprofen. No serious abnormalities in laboratory values were noted.