OBJECTIVE To determine whether alveolar volume (V(A)) measured during the single-breath diffusing capacity for carbon monoxide (DCO) can be used as a substitute measure for the multiple-breath total lung capacity (TLC) in subjects with and without airways obstruction. METHODS Retrospective review of pulmonary function test (PFT) results. METHODS Pulmonary function laboratories at the Johns Hopkins Hospital (JHH) and the Johns Hopkins Asthma and Allergy Center (HAAC). METHODS Patients referred for spirometry, helium lung volumes, and Dco during a single visit between November 1993 and November 1996. RESULTS JHAAC patients (n=2,477) were used to assess the relationship between V(A) and TLC. In patients with an FEV1/FVC > or = 0.70, there was good agreement between V(A) and TLC (V(A)/TLC=0.97 to 0.99). However, in patients with an FEV1/FVC <0.70, V(A) systematically underestimated TLC (V(A)/TLC=0.67 to 0.94). The degree of underestimation was related to the severity of airflow obstruction. To predict TLC using V(A) a regression equation was used to "correct" V(A) for the severity of obstruction. This equation was used to predict the multiple-breath TLC for JHH patients (n=2,892). Patients with an FEV1/FVC > or = 0.70 showed a high degree of correlation between V(A) and TLC (Pearson's correlation coefficient [r]=0.96 to 0.99; p<0.05). After adjusting for the severity of airflow obstruction, patients with an FEV1/FVC in the range of 0.40 to 0.70 also had a strong correlation between the corrected V(A) and the multiple-breath TLC (r=0.83 to 0.94; p<0.05). CONCLUSIONS V(A) accurately predicts TLC in patients with mild or no airflow obstruction. For patients with moderate to severe obstruction, correcting V(A) for the severity of obstruction improves the accuracy of this relatively simple and rapid technique for measuring TLC.