The effect of leukaemia inhibitory factor (LIF) in modulating cholinergic and sensory nerve function was examined using guinea-pig tracheal explants. Specific LIF receptors (LIFR) were immunolocalized to both cholinergic and sensory nerves. Release of SP in culture was not influenced by LIF. Similarly, maximum contraction to carbachol (C-max) was not influenced by LIF. After 3 h, maximum (E-max) eNANC-induced contraction in controls was 32 +/- 2.5% of C-max. In LIF-treated preparations, E-max was enhanced to 50 +/- 4.5% C-max (P <0.05). Cholinergic nerve-induced contractions after 3 h incubation with LIF were similar to control. After 24 h, control E-max was 25 +/- 4.5% C-max (58% smaller than E-max at 3 h). In contrast, in LIF-treated preparations, E-max was 37+2.5% C-max, (24% smaller than at 3 h, P <0.05). This did not appear to be due to the effect of LIF on muscarinic Mt receptor expression or function. Thus LIF appears to differentially influence the function of airway nerves and thus may provide an important link between the immune and neural systems.