Calcinosis, Paget's disease, and arteriosclerosis are three systemic disturbances in which the etiology and pathogenesis are not well understood. Anything which may contribute to our knowledge of these conditions merits serious consideration. The purpose of this presentation is to report two unusual cases of pseudoxanthoma elasticum associated with systemic manifestations and to arrive at a possible pathogenesis for this process. In the first patient the cutaneous changes were widely generalized, involving all the skin except the scalp, palms, and soles. There was also extensive peripheral vascular disease and widespread calcification of the major blood vessels, as well as extensive calcinosis of the subcutaneous tissues of the lower extremities with gangrene. The second patient had Paget's disease associated with angioid streaks and pseudoxanthoma elasticum. It is now well recognized that pseudoxanthoma elasticum is a cutaneous expression of a generalized disturbance (probably genetic) of some