In an eight-week double-blind study comparing the new long-acting aspirin derivative, diflunisal, in doses up to 1 g/day with aspirin in doses up to 4 g/day in 16 patients with classical or definite rheumatoid arthritis, diflunisal was more effective in reducing the total articular index (Ritchie) and erythrocyte sedimentation rate and in increasing grip strength. Diflunisal had an earlier effect on erythrocyte sedimentation rate than antiinflammatory doses of aspirin. Patients on diflunisal experienced fewer side effects than patients on aspirin. Ten patients with rheumatoid arthritis who previously participated in the eight-week study comparing diflunisal to aspirin (five patients from each group) were continued on 1 g diflunisal per day for six months. The efficacy of diflunisal therapy persisted during a six-month period, and there were no side effects. The switchover from 4g aspirin to 1g diflunisal a day was accompanied by further improvement in the Ritchie total score, erythrocyte sedimentation rate, and grip strength and by disappearance of side effects. Diflunisal 1 g/ day proved to be an efficient and well-tolerated drug in patients with rheumatoid arthritis.