This study addressed the question of whether variations in the volume of alveoli and alveolar ducts forming single units of ventilation can significantly influence the distribution and uptake of inspired reactive gases. Quantitative serial section analyses of vascular perfusion-fixed rat lungs were used to determine the anatomic dead space proximal to specific ventilatory units as well as the gas volume of these ventilatory units. Three reconstructions, each consisting of ventilatory units distal to a specific bronchus, were carried out. The number of ventilatory units for each reconstruction varied from 26 to 71. The average ventilatory unit volume for the three reconstructions [0.53 +/- .03 (SE) mm3] was not significantly different from measurements based on random sampling. The distribution of ventilatory unit volume was diverse, with 15% of the population having a volume less than 0.3 mm3 and 9% of the population having a volume greater than 1.0 mm3. For a gas of relatively low reactivity (e.g., oxygen) the predicted oxygen uptake per unit surface area did not vary significantly between ventilatory units. The predicted oxygen uptake was approximately 92% of the uptake in the absence of gradients in oxygen concentration between ventilatory units. For a highly reactive gas (e.g., ozone), the predicted uptake per unit surface area in the proximal portions of larger ventilatory units was significantly greater than the average uptake. These results suggest that focal areas of injury likely result from exposure to inhaled reactive gases.