Administration of Bordetella pertussis vaccine simultaneously with the immunization of rats with guinea pig encephalitogenic protein in Freund's complete adjuvant results in the development of hyperacute encephalomyelitis in the Lewis strain, a strain which reacts with ordinary experimental autoimmune encephalomyelitis (EAE) when immunization is performed without pertussis vaccine. A marked augmentation of the EAE response was seen with pertussis vaccine in the Fischer and PVG strains, both low responders without pertussis, and relapsing EAE developed in some animals. Hyperacute EAE did not develop, however. No effect was seen on the resistant BN strain, but strong EAE developed in the otherwise low-susceptible F1(BN X F) and the practically resistant F2(BN X F) hybrids - in the latter hybrids, EAE developed only when Ir-EAE genes linked to AgB 1 were present. In the F1 hybrids, pertussis vaccine could be given from 4 days before to 5 days after the immunization and an effect was still seen, although a maximal effect was seen when the vaccine was given at 0 or 2 days after immunization.