Sixty patients with active rheumatoid arthritis (mean ESR = 51 mm/h) were treated for six months with D-penicillamine (15 patients), sodium aurothiomalate (15 patients), hydroxychloroquine (15 patients) or enteric-coated aspirin (15 patients). The three groups receiving specific anti-rheumatoid therapy were also allowed enteric-coated aspirin in the dose of their choice as the only “back-up” drug; the group treated with aspirin alone was encouraged to take the maximum tolerated dose. The mean duration of treatment tolerated by patients receiving aspirin alone was 12.3 weeks. Only four patients completed a 24-week treatment period and no improvement was seen in acute-phase reactants. Those patients receiving an anti-rheumatoid drug showed serial improvement in ESR as the dose of aspirin required fell. Plasma salicylate concentrations correlated well with aspirin dosage. Even as an enteric-coated formulation, aspirin alone is not the treatment of choice for active rheumatoid disease.