Using a double-beam stopped-flow apparatus estimations were made of the velocity constant for the initial uptake of oxygen by fully reduced erythrocytes (k'(c)). Mammalian cells were studied with volumes varying from 20 micro(3) (goat) to 90 micro(3) (man), as were bullfrog cells (680 micro(3)). Measurements were made under physiological conditions of pH, P(CO2), and temperature. In man k'(c) was 80 mM(-1) sec(-1) and in other species smaller cells generally had a greater value for k'(c) than did the larger cells. In the goat it was 1.8 times as great as the human value; in the bullfrog it was only one-fifth as great. These differences could not be accounted for by interspecific differences in hemoglobin kinetics. The differences probably represent a true effect of size conferring some biological advantage on the species with the smaller cells. The cell membrane offered resistance to oxygen passage. Using the usual red cell model of an infinite sheet of reduced hemoglobin, membrane permeability appeared to differ among mammals. If, as is likely, the effective cell halfthickness differs among mammals, actual membrane permeability differences may be less. A method for measurement of oxygen saturation of dilute cell suspensions is also described.