This study was designed to examine the inflammatory process in the central and peripheral airways of surgically resected lungs from asthmatic and nonasthmatic subjects. Lung specimens were inflated with cryoprotective, rapidly frozen, and systematically sampled. Cryosections prepared from frozen tissue blocks were fixed in acetone/methanol and immunostained with monoclonal antibodies by using the alkaline phosphatase-anti-alkaline phosphatase technique to detect CD3 (T cells), major basic protein (total eosinophils), EG2 (activated eosinophils), anti-tryptase (mast cells), anti-elastase (neutrophils), and CD68 (macrophages). All airways from patients with asthma demonstrated a significant increase in the numbers of T cells and total and activated eosinophils compared with airways from nonasthmatic subjects (p < 0.001). In the patients with asthma, the numbers of activated eosinophils but not T cells were significantly greater in airways with an internal perimeter less than 2 mm compared with those with an internal perimeter greater than 2 mm (p < 0.05). There were also significantly higher numbers of major basic protein-positive eosinophils, when expressed as a fraction of the alveolar wall tissue, in patients with asthma compared with control subjects (p < 0.05). In asthmatic airways with an internal perimeter of more than 2 mm, there was a greater number of activated eosinophils in the tissue between the epithelium and the smooth muscle compared with the tissue between the smooth muscle layer and lung parenchyma (p < 0.05). In contrast, there was a greater number of total eosinophils in the outer airway layer compared with the inner airway layer (p < 0.05). These results show that there is a similar but more severe inflammatory process present in the peripheral compared with the central airways of patients with asthma, which is consistent with the fact that the smaller airways are a major site of obstruction in asthma.