Recent studies have raised the possibility that biophysical properties of the neutrophil, specifically cell size and deformability, along with the unique hemodynamic properties of the pulmonary microvasculature may be important determinants of neutrophil transit through the lung and lead to significant retention in capillaries. Additionally, accumulating evidence supports the concept that leukocytes may emigrate into inflammatory lesions through the pulmonary capillary wall, quite unlike the situation in the systemic circulation where the predominant site of margination and emigration is the postcapillary venule. To confirm and extent this suggestion, morphometric techniques were employed to determine the location and kinetics of neutrophil movement from the vascular compartment to the alveolar space in response to an inflammatory reaction initiated by local instillation of fragments of the activated form of the fifth component of complement (C5f). We found that the site of neutrophil sequestration and probable migration was almost exclusively the capillary. Neutrophil sequestration appeared first in the capillaries of the interalveolar septae, with negligible accumulation in arterioles and venules (less than that in interalveolar septae by a factor of 10(4) when corrected for the relevant surface areas). Accumulation in the airspaces lagged behind that in the interalveolar septa by about 60 min, placing an upper time-limit on the emigration process across the epithelial barriers. Interestingly, neutrophils samples by bronchoalveolar lavage represented only 1 to 2% of those neutrophils shown to be present in the airspaces of the lung by morphometric assessment, suggesting that bronchoalveolar lavage may sample only a subpopulation of the emigrated cells.(ABSTRACT TRUNCATED AT 250 WORDS)