Sixteen patients with classical rheumatoid arthritis which had been present for longer than two years, representing anatomic stages II-IV, were treated with azathioprine in doses of 50 to 175 mg/day. They were followed up for up to six years. Using the criterion of ability to work, 93% of the patients improved markedly during the time observed. Complement levels were low before treatment and tended to stabilize within the normal range as the disease became less active. Erythrocyte sedimentation rate (ESR) fell during therapy but changes in ESR did not correlate well with the patients' clinical states. Titers of rheumatoid agglutinins showed little change after as long as six years of therapy. When all patients were stable a double-blind cross-over study, using a placebo tablet, was instituted. Fifteen of 16 patients had a marked exacerbation of disease activity after receiving placebo for three to eight weeks. When azathioprine was reinstituted, gradual improvement again occurred so that all patients were back to their asymptomatic or mildly symptomatic state within seven months.