The efficacy of d-2-(6'-methoxy-2'-naphthyl)-propionic acid (naproxen) in the treatment of patients with rheumatoid arthritis as well as its good tolerance has been established in double-blind studies which have been conducted in 34 centers in the U.S.A. Since the value of a new antirheumatic drug can only be assessed after years of clinical experience, provision was made in the protocols of the double-blind studies that the patients completing the controlled studies could continue naproxen treatment. Our experience is based on 603 patients, of whom 337 came from controlled, and 266 from previous open studies. The longest treatment with naproxen lasted four years. 16% of the patients discontinued therapy because of a exacerbation of their symptoms, and 8% because of side-effects, the latter being described in detail. Follow-up examinations of the patients were performed 4841 times at bi-monthly intervals. The statistical analysis of the objective disease symptoms showed a significant decrease of the rheumatic manifestations. In order to exclude the possibility of a long-term placebo effect, and as a proof of continuing efficacy, 73 patients received double-blind placebo instead of naproxen (placebo pulse) for two weeks, whereas the others continued on naproxen. Statistical analysis of the objective symptoms during the two treatment phases of the study showed naproxen significantly superior to placebo in all disease manifestations. Symptoms of those patients receiving placebo aggravated rapidly. They improved again after naproxen was resumed. The situation was reverse in those patients who received placebo during the second phase of the study. Side-effects were observed 13 times under placebo, but only two times under naproxen. The integration of a 2-week-placebo-pulse during long-term naproxen therapy of patients with rheumatoid arthritis is a sensitive method to prove the continuing therapeutic efficacy of this drug.