Pseudoxanthoma elasticum (PXE) is a disorder of connective tissue in which abnormalities of elastic tissue and collagen are found. The purpose of this study was to examine the ultrastructure and distribution of connective tissue components in lesional and non-lesional skin of patients by means of indirect immunofluorescence, electron microscopy and indirect immunoelectron microscopy. Prominent abnormalities of elastic tissue were seen on electron microscopy and confirmed by immunoelectron microscopy. Abnormal elastic fibers containing electron-dense bodies and holes were seen even in non-lesional skin. In addition, the normal pattern of collagen bundles was disrupted in lesional skin, but not in non-lesional skin of patients with PXE. The majority of individual collagen fibrils appeared normal by electron microscopy. The distribution of type IV collagen and laminin was normal in small blood vessels. Finally, abnormalities in the distribution of fibronectin were seen. The finding of atypical elastic fibers in non-lesional skin supports an early role for elastic tissue components in the pathogenesis of PXE. Interactions between elastin, collagen and other matrix substances may explain some of the abnormalities seen.