In 34 patients with emphysema, 12 patients with pulmonary insufficiency from other causes, and 14 normal subjects, arterial Po2, Pco2, and pH were measured when inspired oxygen concentration was 21%, 24%, 28%, 35%, 40%, and 100%, The dead space to tidal volume ratio was measured during ambient air breathing in all, as was venous admixture in 21 patients and 8 normals. An explanation based on variability of the abnormality of alveolar ventilation to blood flow ratio is offered for the known wide variation in the response of arterial Po2 to inspired O2 concentrations among patients with pulmonary disease. Linear regressions are described that allow estimation of response to a given oxygen concentration based on measurement of arterial Po2 during air breathing. These regressions apply to a variety of chronic lung diseases, suggesting similarities in the distribution of low ratios of alveolar ventilation to blood flow in chronic pulmonary disease regardless of etiology.