In a long-term study we have been comparing biochemical changes in the blood of patients with classical or definite rheumatoid arthritis (RA) when groups of patients are treated for the first time with specific anti-rheumatoid drugs for a six-month period. One such group was treated for 26 weeks with azathioprine. Biochemical and clinical assessments were made at each of 10 clinic visits during the treatment period. Side-effects prevented six patients completing the study. Clinical improvement in the remaining patients was accompanied by a reduction in acute phase proteins, increases in total serum sulphydryl and serum histidine, but little or no change in immunological variables. Comparison of correlation matrices constructed between clinical and laboratory variables for azathioprine and drugs previously tested suggests that azathioprine is more effective than a control group on aspirin alone and in some ways comparable with D-penicillamine.