A total of 42 patients participated in three controlled clinical trials, each of different design, to demonstrate the efficacy and safety of naproxen in the treatment of rheumatodi arthritis. First, a double-blind comparison of aspirin and naproxen was made in 24 patients. As judged by objective and subjective measurements of disease activity, naproxen was at least as effective as aspirin and the incidence of severity of side effects were less with naproxen than with aspirin. Second, the safety and efficacy of naproxen administration was followed in 42 patients for up to two years. Third, the continued efficacy of naproxen during these two years was tested by interspersing a short period of double-blind placebo administration for some patients. The observations made in this clinical study suggest that naproxen is an effective and well-tolerated drug in the long-term treatment of rheumatoid arthritis.