• Isoniazid given thrice daily in 100-mg. capsules was compared with a placebo as to its effects on patients with multiple sclerosis. Special efforts were made to verify the diagnosis, avoid unnecessary risks to the patient, extend the period of observation sufficiently to provide a real test, include enough patients in whom the disease had been recently active, and eliminate bias through randomization and double-blind procedures. The 186 patients finally selected were enrolled in 11 hospitals; 88 received isoniazid and 98 received the placebo. In evaluating the results each patient was rated as to the severity of his symptoms according to the modified Kurtzke scale before and after the period of medication; the patient was also rated as to a variety of specific neurological changes, self-care score, and ambulation score. By all criteria, including laboratory findings and over-all clinical impressions, the differences between the isoniazid and placebo groups were insignificant. No beneficial effects that could be ascribed to isoniazid in multiple sclerosis were observed in nine months or more of follow-up.