The aim of this study was to test whether a large surface to volume ratio of the red blood cells is advantageous for O 2 transfer in lungs. Suspensions of washed large (human) and small (sheep) red blood cells were used to perfuse in random order isolated cat lungs ( n = 7). The lungs were kept at 27°C, ventilated with 1.01/min and perfused with 110 ml/min. Hemoglobin concentration was 70 g/l. Assuming an inhomogeneous lung with an alveolar dead space compartment, pulmonary diffusing capacity for O 2 (D L O 2 ) was 0.53 ± 0.10 ml · min −1 · mmHg −1 ( mean ± SD) when perfusing with sheep red cells and 0.52 ± 0.13 with human red cells. On the basis of a lung model with a low V̇ A/Q̇ and a high V̇ A/Q̇ compartment the values were 0.86 and 0.93. Thus, D L O 2 was not larger with smaller red blood cells, i.e. with higher red cell surface area per blood volume. Possible explanations for this unexpected result are discussed.