Infection and inflammation are accompanied by fever, neuroendocrine activation and alterations in behaviour and mood. It is commonly accepted that these non specific symptoms are mediated by blood-borne mediators acting on the brain. These mediators include proinflammatory cytokines such as IL-1, IL-6 and TNF. In this paper, we present new evidence indicating that this view is inadequate and that the proinflammatory cytokines which are released at the periphery by activated accessory immune cells act on the brain via a neural pathway involving activation of peripheral sensory nerves.