To investigate the interaction between the peripheral nervous and the immune system in vivo, we used two mouse models of T cell and TNF-alpha dependent liver injury inducible by either concanavalin A or a combination of D-galactosamine and staphylococcal enterotoxin B. Mice depleted of peptidergic sensory nerve fibres by capsaicin were protected from liver injury. Moreover, TNF-alpha production was significantly reduced. Examination of the effect of catecholamines on liver injury showed that the beta2-adrenergic agonist salbutamol prevented, whereas chemical sympathectomy by 6-hydroxydopamine, deteriorated the disease. Hence, strategies reducing the activity of peptidergic sensory nerve fibres or stimulating beta2-adrenoreceptors, may be of benefit in immune-mediated liver disease.