We have previously reported that the magnitude of deep inspiration (DI)-induced bronchodilation is only slightly reduced in mild asthmatics, compared to healthy subjects. The aim of this study was to evaluate whether increased severity of asthma is associated with impairment in the ability of DI to induce changes in lung volume. Thirty-six consecutive asthmatics recruited from the Pulmonary and the Allergy Outpatient Clinics of the Institute of Respiratory Diseases of the University of Palermo were divided into 3 groups: Intermittent (I), Mild Persistent (MP) and Moderate-Severe (MS), based on GINA guidelines. Single dose methacholine (Mch) bronchoprovocations were performed in the absence of DI, to induce at least 15% reduction in inspiratory vital capacity (IVC) from baseline. The post-Mch IVC was followed by 4 consecutive DI and by another IVC, to determine the bronchodilatory effect of DI. The bronchodilatory effect of DI was found to significantly decrease with increasing severity of asthma (I: 68+/-5.4%, MP: 45+/-7.2%, MS: 4+/-15.6%; ANOVA: P<0.0001). Bronchodilation by DI, but not FEV(1) or FEV(1)/FVC, was also inversely correlated to symptom scores (r=-0.42, P=0.01) and to weekly salbutamol usage (r=-0.47, P=0.004). These observations provide support to the hypothesis that the attenuation of the bronchodilatory effect of DI contributes to the severity of the clinical manifestations of asthma.