Seventeen patients with classic rheumatoid arthritis resistant to conventional therapy were treated in a double-blind, cross-over study with azathioprine (2.0 to 2.5 mg/kg/day) and placebo for two 16-week periods. Patients receiving azathioprine showed significant improvement in articular index, joint count, grip strength and effusions, manifest by 6 weeks but greater at 16 weeks. Erythrocyte sedimentation rate and latex titer did not change. White blood cell counts decreased on azathioprine, but normal counts did not preclude a response. Rash, nausea and hair thinning occurred in only 4 patients.