The characteristic histopathologic lesion of pseudoxanthoma elasticum (PXE) is calcification of the central core of elastic fibers in affected organs; it is correlated with clinical severity. One hypothesis holds that lowering dietary calcium might reduce or prevent tissue injury and minimize clinical effects. This hypothesis would be supported by demonstrating that clinical expression is positively associated with previous calcium intake. We studied 32 unrelated PXE patients (20 men and 12 women, mean age 43 years, SE = 14.2, range = 13-71) by grading their clinical severity and their presumed calcium intake during childhood, adolescence, and adulthood. Overall severity in the study group varied greatly and correlated positively with age (P less than 0.001). Overall severity correlated positively with calcium ingestion as an adolescent (P less than 0.001, with the other predictor variables held constant). Overall cardiovascular and eye severity were a function of age (P less than 0.000001 for both), whereas skin severity was not. These results confirm that PXE is a highly variable condition that generally worsens with age and support the rationale for a clinical trial to determine the effects of different levels of dietary calcium ingestion in young PXE patients on their subsequent clinical course.