Autopsies were performed in three cases of pseudoxanthoma elasticum (PXE) to evaluate the cardiovascular changes. The endocardial lesion characterized by intimal fibroelastotic thickening and disorganization, fragmentation, and calcification of elastic fibers in the deeper endocardial layers is unique histologically. Severe atherosclerosis was present in all cases and resembled that encountered routinely. Fragmentation and degeneration of the elastic laminae of muscular arteries was followed by vascular calcification that could not be distinguished morphologically from Mönckeberg's arteriosclerosis. All three cases showed striking initimal fibroelastotic thickening, particularly in intrarenal arteries, resembling that seen in hypertension, although only one of the subjects was hypertensive. It would appear that the metabolic defect in PXE predisposes to the premature onset and accelerated development of commonly encountered vascular aging processes, and that the endocardial lesion is the only specific cardiovascular manifestation of the disease.