To test specificity of the involvement of vagal afferents in the communication between the immune system and the brain, sham-operated and vagotomized mice were injected i.p., s.c. or i.v. with physiological saline or interleukin-1 beta (IL-1 beta [symbol: see text] 4 weeks after surgery. Vagotomy attenuated the decrease in social exploration induced by i.p. injection of 300 ng recombinant human IL-1 beta but had no effect when IL-1 beta was injected s.c. (300 ng) or i.v. (500 ng). Vagotomy also attenuated the depression in social investigation induced by i.p. injection of recombinant rat IL-1 beta (IL-1 beta, 1 microgram) but was without effect when 1 microgram IL-1 beta was injected i.v. These results confirm the role of vagal afferent nerves in the transmission of an immune message from the periphery to the brain and show that the vagus nerve only conveys information concerning cytokines injected into the abdominal cavity.