In order to study neutrophil traffic in the lungs of humans, we harvested autologous neutrophils and radiolabeled them with indium-111 prior to reinjection. The passage of these [111In]neutrophils through the pulmonary vasculature was compared with that of [99mTc]erythrocytes in normal elderly subjects and in patients with chronic obstructive pulmonary disease (COPD). Neutrophil sequestration within the lungs of seven normal subjects, 10 min after reinjection, correlated with local erythrocyte transit times in the lungs (tau = 0.72, p less than 0.001). This relationship was lost in patients with COPD. In seven patients studied during an acute exacerbation of COPD, neutrophil retention was higher during the first passage through the lungs (mean, 22.0 SD 14.1%) compared with 14 patients studied when their condition was stable (16.3 SD 3.4%, p less than 0.001), or to the normal elderly subjects (13.7 SD 7.0%, p less than 0.001). In addition, the subsequent rate of neutrophil washout from the lungs was slower in patients with acute COPD (1.93 SD 0.66 x 10(-3)s1) than in those with stable disease (3.08 SD 1.8 x 10(-3)s-1, p less than 0.02). Neutrophil retention in the lungs correlated inversely with the extent of emphysema, assessed quantitatively by CT scanning (tau = 0.68, p less than 0.05). Thus, patients presenting with acute exacerbations of COPD have an increased neutrophil burden in the pulmonary vasculature with the potential for increased lung proteolysis.