The use and tolerance of cyclosporine A (Cy A) and azathioprine (AZA) are compared as long-term immunosuppression treatment for multiple sclerosis. 38 patients with multiple sclerosis were randomized and received either Cy A (5 mg/kg/d) or AZA (2 mg/kg/d) during 24 months. These patients were assessed clinically and with different biological parameters. The Cy A blood level was controlled, and Cy A was well tolerated without side effects forcing to stop the treatment. However, its benefits were limited when the different clinical scores are compared.