Plexogenic pulmonary arteriopathy runs a more progressive course in transposition of the great arteries with pulmonary hypertension (TGA) and in primary pulmonary hypertension (PPH) than, for instance, in isolated ventricular septal defect (VSD). Fibrinoid necrosis and plexiform lesions occur more often and at a younger age in TGA and PPH than in VSD. A morphometric study in 18 patients with VSD, 14 patients with TGA, 38 patients with PPH, and 21 controls showed that the media of muscular pulmonary arteries is significantly thicker in VSD than in TGA or PPH, with the sole exception of very young children with PPH. This difference in medial thickness is apparent at any level of pulmonary arterial pressure. Conversely, the more advanced pulmonary vascular lesions were particularly prominent in TGA and PPH. It is likely that medial hypertrophy, at least to a certain extent, protects the pulmonary arteries from the development of more ominous vascular alterations.