In summary, we have shown here that IL-1 contributes to acute pathology after intramuscular immunization with VSV. IL-1 was not required for control of viral replication, for the induction of cellular or humoral immune responses, or for development of protective immunity to rechallenge. These results add to our understanding of the role for IL-1 in promoting immunity to viral challenge, and support the notion that the requirement for IL-1b in promoting adaptive immunity may vary according to the type and dose of pathogen encountered as well as the route of exposure. Finally, by identifying IL-1b as a major source of reactogenicity for rVSV vaccines, we are able to propose a novel strategy to ameliorate side effects without compromising immunogenicity.