Interleukin-1β (IL-1β), a cytokine released by activated immune cells, elicits various illness symptoms including hyperthermia. Previous hypotheses to account for these actions have focused on blood-borne IL-1β exerting its effects directly at the level of the brain. However, recent behavioral and physiological evidence suggest that IL-1β can activate the subdiaphragmatic vagus. The present experiments demonstrate that subdiaphragmatic vagal transection disrupts the hyperthermia-inducing effects of recombinant human IL-1β and stress. These data provide evidence for a novel route of immune-brain communication, as well as a novel route whereby stress can influence physiological processes.