To investigate whether or not the pathologic features in the lungs of patients with chronic obstructive pulmonary disease (COPD) are related to the gas exchange response during exercise, we studied 17 patients (15 men, two women) with mild-to-moderate airflow obstruction (FEV1/FVC ratio, 59 +/- 3%), undergoing resective lung surgery, at rest and during submaximal exercise (71 +/- 5% predicted VO2max). During exercise, arterial PO2 increased (from 81 +/- 3 to 86 +/- 3 mm Hg, p less than 0.05) as a result of an overall improvement in VA/Q relationships. This improvement included an increase in the mean VA/Q ratios of both ventilation and blood flow distributions, and a more homogeneous ventilation distribution (logSD V, from 0.66 +/- 0.06 to 0.50 +/- 0.03; p less than 0.01; normal value, less than or equal to 0.6). The morphologic evaluation of the resected specimens disclosed a moderate degree of emphysema (emphysema score, 16 +/- 4) and mild abnormalities in membranous bronchioles (total pathology score, 107 +/- 8). At rest, significant correlations were found between the severity of the pathologic findings and both the degree of hypoxemia and the extent of VA/Q mismatching. During exercise, no relationship between bronchiolar abnormalities and gas exchange measurements was observed, whereas the severity of emphysema was correlated with PaO2 (r = -0.54, p less than 0.05). Both the overall increase in and the more efficient distribution of ventilation accounted for the improvement in VA/Q distributions during exercise. These changes were more pronounced in patients with a greater degree of bronchiolar abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)