In patients with secundum atrial septal defect, pulmonary hypertension appears to be attributable to microatelectasis of the lung. To confirm this hypothesis, pulmonary arteries in surgical biopsy specimens from 72 patients with atrial septal defect and pulmonary hypertension were subjected to morphometric examination. Thirty eight of the 72 patients (53%) were found to have microatelectasis of the lung, which suggests that an even higher frequency would have been found if the entire organ had been examined. Atelectatic changes were found in 21 of 39 patients with plexogenic pulmonary arteriopathy (54%), 8 of 15 with musculoelastosis (53%), and 9 of 13 with both of these lesions (69%). No such changes were observed in 5 patients with atrial septal defect who showed thromboembolism-type lesions of the pulmonary arteries. On the other hand, microatelectasis was not observed in another 5 patients with atrial septal defect who did not exhibit pulmonary hypertension. The medial smooth muscles of pulmonary arteries in atelectatic areas were thicker (16.4 +/- 4.0 microns) than those in non-atelectatic areas (10.3 +/- 3.3 microns). The index of pulmonary vascular disease was not significantly different between atelectatic (2.0 +/- 0.6) and non-atelectatic areas (1.9 +/- 0.5). We conclude that in microatelectatic areas, which may tend to develop after respiratory infections in patients with atrial septal defect, hypoxic vasoconstriction of the small pulmonary arteries is liable to occur, which causes hypertrophy of the media. This is likely to lead to the elevation of pulmonary arterial pressure and sustained pulmonary hypertension.