In two preliminary trials, thymectomy was performed on 35 multiple sclerosis (MS) patients, with (Group I) or without (Group II) azathioprine therapy for 1 year. Formal studies of clinical neurologic status were conducted at yearly intervals after operation. Each group was compared with carefully matched control patients. Group I patients showed significant improvement in total functional groups (Kurtzke scale) and pyramidal functions 1 and 2 years following thymectomy. Other individual functions showed no significant difference. There was a statistical improvement in disability status (Kurtzke) for patients with relapsing-remitting MS 1 and 2 years following thymectomy. This subset also had a significant decrease in MS exacerbations. Group II patients showed none of the favorable trends seen in Group I. Functional groups, disability status scale, and exacerbations were similar to those of the control patients. Several studies indicate azathioprine therapy alone is of questionable benefit in MS. In the myasthenia gravis (MG), the full immunosuppressive effect of thymectomy may not be realized for several years. Therefore, it is possible that in Group I patients a dual mechanism of immunosuppression - azathioprine and thymectomy - is yielding a favorable response not yet apparent in the Group II patients having thymectomy alone. If our data still appear favorable after a third follow-up year, a formal pilot study will be undertaken.