The kinetics of O2 uptake into and release from human erythrocytes was investigated at 37 degrees C by a stopped-flow technique. From the time course of O2 saturation (SO2) change a specific transfer conductance of erythrocytes for O2 (GO2) was calculated. The following results were obtained: 1) GO2 decreased in the course of O2 uptake, but initial GO2 was nearly independent of SO2 at which uptake started; 2) addition of albumin to the medium reduced GO2; 3) increasing dithionite concentration in the medium in O2-release experiments progressively enhanced GO2, which became virtually constant for nearly the entire course of release; and 4) O2 uptake and O2 release (without dithoite) in the same SO2 range yielded very similar GO2. These results suggested that O2 uptake and release were importantly limited by diffusion through the external medium and that in the SO2 range between 0.3 and 0.8, chemical reaction exerted little limiting effect. Since O2 release at the highest dithionite concentration (40 mmol/l) appeared to be virtually unlimited by external diffusion, GO2 measured under these conditions, averaging 8.7 ml X min-1 X Torr-1 X ml erythrocytes-1, was considered to mainly reflect intracellular diffusion limitation. The corresponding specific transfer conductance for O2 transfer in whole blood (hematocrit, 0.45) is 3.9 ml X min-1 X Torr-1 X ml blood-1.