Examination by electron microscopy of the elastic fibers of individuals with Pseudoxanthoma Elasticum (PXE) revealed that the principal alterations were in the elastin moiety of the elastic fibers. The elastin had a granular appearance, an increased affinity for cationic stains, and it often demonstrated sites of increased density presumed to represent foci of calcification. In contrast to the elastin, the microfibrillar component of the elastic fibers was unchanged, both in morphologic appearance and in distribution. There was no clear correlation between the extent of the morphologic alteration in the elastic fiber and the level of clinical severity. Morphologically altered fibers were often found together with unaltered fibers. Changes similar to those seen in patients with PXE were also found in biopsies obtained from clinically unaffected consanguinous relatives. The pattern of inheritance in several of the families examined was compatible with autosomal recessive, whereas in at least one family a more complex mode of transmission seems likely. The electron microscopic data therefore provide further support for the genetic heterogeneity of PXE.