Tumour necrosis factor-α (TNFα) is implicated in the pathogenesis of asthma; however, little is known of its direct effect on smooth muscle reactivity. We investigated the effect of TNFα on the responsiveness of human bronchial tissue to electrical field stimulation in vitro. Incubation of non-sensitized tissue with 1 nM, 3 nM and 10 nM TNFα significantly increased responsiveness to electrical field stimulation (113 ± 8, 110 ± 4 and 112 ± 2% respectively) compared to control (99 ± 2%) (P < 0.05,n = 6). Responses were not increased in sensitized tissue (101 ± 3% versus 105 ± 5%, n = 3, P > 0.05) nor were responses to exogenous acetylcholine (93 ± 4% versus 73 ± 7%, n = 3, P = 0.38). These results show that TNFα causes an increase in responsiveness of human bronchial tissue and that this occurs prejunctionally on the parasympathetic nerve pathway. This is the first report of a cytokine increasing human airway tissue responsiveness.