For rVSV-based vaccines to move forward to clinical use it is important to identify ways to eliminate rVSV vector-associated pathology that do not at the same time compromise vector immunogenicity or oncolytic properties. It has been shown previously that TNF-a produced in response to intranasal immunization with rVSV vaccine vectors contributes to, but is not the only factor responsible for, rapid weight loss after rVSV immunization [14] . In those studies, TNF-a deficient mice were partially protected from acute pathology after VSV challenge, and TNF-a was not required for the generation of humoral immune responses to rVSV [14] . We undertook the present study to expand on those observations, focusing on the importance of IL-1. We addressed intramuscular immunization, because that is the most likely route of administration for rVSV vectors in humans.