Neurokinin (NK) A causes airway narrowing in patients with asthma through direct and indirect mechanisms. The effects of the inhaled glucocorticosteroid fluticasone propionate (FP) on the bronchial responsiveness to NKA and methacholine were studied. Patients (n=11) with mild asthma participated in a randomized, double-blind, placebo-controlled crossover trial. FP (500 microg b.i.d.) or matched placebo was administered via Diskhaler for 14 days. Bronchial challenges were performed on days 1 and 13 (methacholine) and 0 and 14 (NKA) for each treatment period. At the active treatment period, the mean log2 provocative concentration causing a 20% fall in the forced expiratory volume in one second (PC20)+/-SEM for NKA was -12.72+/-0.63 at the beginning and -9.77+/-0.49 at the end of the period (p<0.0001), while under placebo, it was -12.16+/-0.82 and -12.19+/-0.51 respectively (NS). At the active treatment period, the mean log2 PC20 for methacholine was -5.25+/-0.40 at the beginning and -4.22+/-0.31 at the end of the period (p=0.012), while under placebo, it was -5.47+/-0.47 and -5.24+/-0.42 respectively (NS). The reduction in response to NKA was significantly larger than that for methacholine. A 2-week course of an inhaled steroid reduces bronchial responsiveness to neurokinin A, an effect more pronounced than the reduction in bronchial responsiveness to methacholine.