In a double-blind, crossover study, naproxen, 250 mg twice a day, naproxen, 500 mg taken at bedtime, and indomethacin, 25 mg four times a day, were compared in 132 patients with rheumatoid arthritis; six centers participated in the study. Objective indices of arthritis activity, such as number of clinically active joints, walking time, and duration of morning stiffness, were nearly identical for the three treatment regimens. Of particular interest was the observation that efficacy of a single daily dose of naproxen was comparable to that of the twice-daily dosage. Naproxen was better tolerated than indomethacin, as shown by a statistically significant difference in the incidence of CNS complaints.