As physiologic and autopsy evidence suggests that peripheral airways and parenchyma are involved in asthma, we hypothesized that significant alveolar tissue inflammation is present in patients with stable, chronic asthma. Eleven patients with nocturnal asthma (NA) and 10 patients with non-nocturnal asthma (NNA) were studied. Each subject underwent two bronchoscopies with proximal airway endobronchial and distal alveolar tissue transbronchial biopsy in a random order at 4:00 P.M. and 4:00 A.M. Morphometric analysis was used to determine the number per volume (Nv) of inflammatory cells. Between-group comparisons showed that the Nv of eosinophils was greater in the NA alveolar tissue 4:00 A.M. compared with the subjects with NNA (40.2 x 10(3) [26.4-57.1 x 10(3), IQ] versus 15.7 x 10(3) [2.1-35.2 x 10(3), IQ], p = 0.05). In regard to the airway biopsies, no difference in the inflammatory and epithelial cells between the two groups was seen at either time. The NA group exhibited greater eosinophils and macrophages in the alveolar tissue at 4:00 A.M. compared with 4:00 P.M. (40.2 x 10(3) [26.4-57.1 x 10(3), IQ] versus 10.3 x 10(3) [2.7-16.8 x 10(3), IQ], p = 0.016 for eosinophils and 215.1 x 10(3) [129.9-356.1 x 10(3), IQ] versus 166.3 x 10(3) [150.7-212.6 x 10(3), IQ], p = 0.031 for macrophages). Only alveolar tissue eosinophils, not proximal airway tissue eosinophils, correlated with the nocturnal decrement in lung function (r = -0.54, p = 0.03). These findings suggest that eosinophils and macrophages accumulate to a greater extent in the alveolar tissue and these changes contribute more to the variation in lung function compared with inflammation in the more proximal tissue.