To test the hypothesis that acute inflammation in peripheral airways can cause changes in airway function, we measured lung mechanics and assessed postmortem histology in 20 dogs. After baseline measurements of subdivisions of lung volume, pressure volume curves, pulmonary resistance (RL), dynamic compliance (Cdyn), closing capacity (CC), and the slope of phase 3 of the single breath N2 washout curve (delta N2/L), 10 dogs breathed nebulized 0.25% HCl (Group 2) and 10 breathed nebulized normal saline (Group 1). Measurements were repeated at 90-min intervals for 4 h. Animals were killed and 1 lung fixed in inflation and sampled for quantitative histology. The severity of the inflammatory reaction was assessed by evaluating the number of polymorphonuclear leukocytes per airway. Wet-to-dry-weight ratios were measured in the other lung. In Group 2, RL, delta N2/L, residual volume, and CC increased, whereas Cdyn decreased after acid inhalation; Cdyn and delta N2/L remained significantly different at the end of the experiment. Bilateral vagotomy, carried out in 5 dogs from each group, did not alter the acid-induced effects in Group 2. There was no difference between groups in wet-to-dry weight ratios. Group 2 had a more severe inflammatory reaction in the peripheral airways than Group 1 (p less than 0.025). We conclude that minimal, acute peripheral airway inflammation is associated with detectable abnormalities in small airway function.