1. 6-Mercaptopurine (6-MP) prevents experimental allergic encephalomyelitis (EAE) during the period of drug administration in both rabbits and guinea pigs. The disease is suppressed even when treatment is started as late as the 5th day after antigenic stimulation in guinea pigs and the 12th day in rabbits. 2. After discontinuation of 6-MP treatment, there is a latent period before the disease is noted. The length of this latent period is not modified by the duration of 6-MP treatment. 3. The effect of 6-MP on EAE is not the result of leukopenia, non-specific toxicity and debilitation, anti-inflammatory activity, or mere masking of clinical signs of the disease. It is, rather, the result of 6-MP's specific anti-immunologic activity. 4. The effects of 6-MP on antibody production, delayed hypersensitivity, and EAE are compared. This provides indirect evidence for the importance of circulating antibody in the pathogenesis of EAE. 5. The important considerations in the use of 6-MP are discussed and the possible usefulness of 6-MP in human neurologic diseases is considered.