The fractional carbon monoxide uptake is the percentage of the inspired carbon monoxide which is absorbed in the lungs. The fractional carbon monoxide uptake (FUco) and pulmonary diffusing capacity (Dco) were measured in 48 normal subjects at rest and during exercise. Measurements at rest were made in 64 patients with chronic chest disease and in 35 of these the tests were repeated during exercise. A modification of the Bates steady-state technique for estimating diffusing capacity is described. The FUco showed no significant differences between men and women and there was no relationship to body surface area. There was a decrease in the FUco at rest with increasing age, but this relationship was not present when the FUco was measured during exercise. The normal FUco had a narrower range than Dco and was relatively little affected by voluntary hyperventilation. The FUco at rest and during exercise in the same individual agreed well irrespective of whether the result was normal or abnormal. A normal FUco corresponded with a normal Dco, and a low Dco was always associated with a low FUco. Where the FUco was low and the Dco was normal, evidence is presented which suggests that the FUco revealed an abnormality of gas exchange which was not shown by the Dco. By interrelating minute volume, Dco and FUco it was possible to divide patients into those with normal gas exchange and those with abnormal gas exchange. The abnormal gas exchange group could be further subdivided into those who did and those who did not successfully compensate for this abnormality.