With the perspective of establishing a link between a respiratory function test and alterations of membranous bronchioles, respiratory bronchioles, and alveolar ducts, we performed forced expirations and four kinds of single-breath washout maneuvers on 27 men due to undergo a lobectomy for peripheral bronchial carcinoma. For the single-breath washouts, the inhaled gas mixture consisted of 90% O2, 5% He, 5% SF6. The four maneuvers were the standard vital capacity test and three successive inhalations of 0.5, 1, and 1.5 L from functional residual capacity. The slopes of N2, He, and SF6 for each maneuver were computed, as well as a new index (I2) describing the relative decrease of the difference between the SF6 and the He slopes induced by a larger inspiratory volume. The histologic analysis focused on pigmentation, inflammation, and fibrosis of membranous bronchioles, respiratory bronchioles, and alveolar ducts. There was a linear relationship with a highly significant correlation coefficient between the new index I2 and the degree of inflammatory (r = 0.73) and fibrotic (r = 0.63) changes of the respiratory bronchioles; this correlation persisted in patients with a normal FEV1/VC ratio. These preliminary data open the way to finding a test for early peripheral (intraacinar) airway dysfunction.