We measured carbon monoxide diffusion capacity (DLCO) in the sitting and supine position in 73 apparently normal subjects (41 nonsmokers and 32 smokers). The coefficient of DLCO standardized for alveolar volume (KCO) was less in the smokers than in the nonsmokers (P less than 0.05) in the sitting position, but the separation was wider in the supine posture (P less than 0.01). The per cent changes between supine and sitting KCO (deltaKCO) were shown to be age dependent in both nonsmokers and smokers, but this age dependence was more accentuated in the latter group. Only 3 smokers were below the 95 per cent confidence limit of nonsmokers for KCO in the sitting position, but there were 7 smokers below that limit for deltaKCO. An attempt was made, using intravenous injection of xenon-133, to study the mechanism of this impairment. Persons who failed to increase KCO in the supine posture showed an ability to increase apical blood flow in that position. The mechanisms of impairment in deltaKCO remain to be explained and may be due either to a predominant apical defect or to a widespread abnormality of the pulmonary capillary bed.