&NA; —We performed a randomized, placebo‐controlled, double‐blind, comparative clinical trial of 36 weeks of methylprednisolone and 3 years of azathioprine in 98 patients in the chronic progression phase of multiple sclerosis (MS). We demonstrated a trend in favor of the combination therapy for limiting progression. The relapse rate in the azathioprine recipients was half that of the control group, and visual evoked potential latencies were stabilized in those who received the combination. We think that a therapeutic trial of continuous use of the combination of adrenal steroids with azathioprine would be worthwhile if administered early in the course of the disease.