The effect of oral linoleic acid (LA) treatment on experimental allergic encephalomyelitis (EAE) in guinea-pigs in three trials of differing disease intensity has been investigated. The efficacy of LA treatment was linked to the severity of the disease being suppressed. The trial with the greatest disease severity showed no beneficial effect. The other two trials with less severe disease showed a marked therapeutic response to LA, but only when treatment was started before immunization and given continuously. This was apparent in both clinical and histopathological responses. These results support an immunoregulatory mechanism for LA treatment in EAE and by analogy in multiple sclerosis.