A study on the resistances to oxygen transport in the microcirculation has been conducted. In Part I of this work, the oxygen permeability of cultured bovine aortic and human umbilical vein endothelial cell monolayers was measured directly in vitro. The monolayers were cultured on silicone rubber membranes and placed in a carefully calibrated diffusion cell immersed in a 37\sp∘C waterbath. The lower and upper chambers of the diffusion cell were filled with well-stirred, degassed saline and flushed with humidified oxygen respectively. The permeability of the endothelial monolayers was determined from the rate of increase of the oxygen partial pressure in the saline, as monitored by a Clark-type polarographic electrode. The lower bound on the permeability of the cultured endothelial monolayer was determined to be 1.42 ± 0.33 (s.d.) × 10\sp−6 cm\sp2/sec for bovine aortic endothelial cells and 1.96 ± 0.52 (s.d.) × 10\sp−6 cm\sp2/sec for human umbilical vein endothelial cells. The best value of the permeability of human umbilical vein endothelial monolayers determined in this work was 8.73 ± 3.21 (s.d.) × 10\sp−6 cm\sp2/sec. This value of permeability indicates that the resistance to oxygen transport in the endothelium is not as high as some previous studies indicate and is not of dominant importance in determining oxygen transport to tissue. In Part II of this work, the effect of hemoglobin S (HbS) polymerization on the oxygen effective diffusivity in sickle erythrocytes was studied at 25\sp∘C using the diffusion cell apparatus. The effective oxygen diffusivity in fully oxygen saturated 10.2 g/dl hemoglobin A (HbA) solution and normal erythrocytes measured in this work were in excellent agreement with prior workers' measurements of diffusivity unfacilitated by hemoglobin. Furthermore, at full oxygen saturation, the effective oxygen diffusivity was not significantly different in sickle and normal erythrocytes. However, when the average oxygen tension in the samples was decreased progressively over the time course of the experiment, the effective diffusivity was significantly different in normal erythrocytes compared to sickle erythrocytes. It can therefore be concluded that HbS polymerization has a significant effect on the resistance to oxygen transport in sickle erythrocytes not fully saturated with oxygen.