The process of pulmonary oxygen uptake is analyzed to obtain quantitative estimates of pulmonary diffusing capacity DLO2. An axisymmetric model is used to represent radial diffusion of oxygen from alveoli through the alveolar-capillary membrane, through the plasma, and into the erythrocytes. Analysis of unsteady diffusion due to the passage of the discrete erythrocytes shows that the transport of oxygen through the alveolar-capillary membrane occurs mainly in the regions adjacent to erythrocytes, and that oxygen transport through regions adjacent to plasma gaps can be neglected. Calculations are performed for a range of discharge hematocrit and capillary diameter values. The model developed above is used to calculate values of DLO2 as a function of capillary diameter and hematocrit. The values obtained range from 50 to 90 ml O2 min-1 mmHg-1, with values at the higher end of the range corresponding to higher hematocrit and lower capillary diameter and therefore a high lineal density of erythrocytes. These values are much lower than the estimates obtained by others using the morphometric method, which considers the total membrane area and the specific uptake rate of erythrocytes. Representing relative resistances in terms of an inverse Sherwood number demonstrates that under normal circumstances, resistances due to intraerythrocyte diffusion, plasma diffusion, and alveolar-capillary membrane are of similar magnitude, and that the transport resistance due to oxygen unloading is negligible. Additional calculations performed for increasing alveolar-capillary membrane thickness demonstrate the expected effect of decreasing lung diffusing capacity. Finally, simulations of pulmonary oxygen uptake based on the new estimates of lung diffusing capacity are consistent with experimental data on oxygen uptake in exercise and hypoxia.