We reviewed medical records from eight patients (4 to 29 years of age) with a functional single ventricle and pulmonary microthrombosis as observed on open lung biopsy specimens. Hemodynamic assessment before biopsy revealed pulmonary hypertension (mean pulmonary artery pressure 19 to 53 mm Hg) in the seven patients tested and severely increased pulmonary arteriolar resistance (6 to 13 U.m2) in three of the five patients in whom these measurements were performed. Pulmonary blood flow varied (< 4 L/min per square meter in two patients and > 5 L/min per square meter in four patients), and the pulmonary/systemic blood flow ratio was low or normal (0.6 to 1.1) in five of six cases. Hemoglobin values were increased (16.4 to 22 gm/dl) in seven of eight patients. Lung biopsy specimens revealed thrombotic obstructive lesions in 56% (range 28% to 96%) of muscular pulmonary arteries. Coexistent medial hypertrophy was absent or mild in all but one specimen, and none had features of plexogenic pulmonary arteriopathy. Microscopic pulmonary thrombi accounted for unexpected pulmonary hypertension, precluding the Fontan operation, in five patients and unsuccessful Fontan operation in two. Clinically significant thrombi should be considered in patients with severe polycythemia (hemoglobin value > 20 gm/dl) and unobtainable or unreliable pulmonary blood flow or pulmonary resistance determinations.