Administration of azathioprine in the diet to Lewis rats reduced the lethality of this drug relative to various regimens by gavage. This mode of administration made it possible to administer effective doses with reduced toxicity. Azathioprine blocked the early development of adjuvant arthritis and decreased the joint scores of animals with established adjuvant disease. A combination of azathioprine and prednisolone produced an additive reduction of both developing and established joint scores. A 10 day pulse regimen of prednisolone resulted in a strong, rapid decrease in established joint scores. This decrease was sustained by continuous administration of azathioprine. In all cases removing azathioprine and/or prednisolone from the diet of animals with established adjuvant arthritis resulted in recurrence of disease. The results of these studies support the validity of the adjuvant model for prediction of anti-arthritic activity.