We investigated the effect of oral administration of type I interferon (IFN) in experimental allergic neuritis (EAN) in Lewis rats immunized with bovine peripheral nerve myelin. Starting at 7 days preceding immunization, rats were fed daily until sacrifice either with 5000 U rat IFN-α/βor mock-IFN. The clinical severity of EAN was significantly reduced in IFN-α/βfed animals compared to mock-IFN fed controls. Demyelination, but not inflammation, was decreased in IFN-α/βfed compared to mock-IFN fed rats at day 20 after immunization.In situIFN-γproduction and inflammation were reduced when evaluated by immunocytochemistry at day 13 after immunization. Spleen cells from IFN-α/βfed compared to mock-IFN fed EAN rats showed significantly reduced proliferation to stimulation with Con A or peripheral nerve myelin. IFN-γproduction in draining lymph node cells was significantly reduced after stimulation with bovine peripheral nerve myelin. Our data suggest that oral administration of IFN-α/βreduces the severity of EAN, possibly by a reduction in production.