For the first half of the twentieth century, the published reports on primary pulmonary hypertension (PPH) were confined to clinical pathological correlations. In the 1950s the physiological aspects began to be reported followed by epidemiologic studies triggered by an epidemic of PPH due to the ingestion of an appetite suppressant, aminorex fumarate. The epidemic prompted a series of meetings of the World Health Organization, which led, in turn, to the creation of the U.S. Registry of Primary Pulmonary Hypertension, standardization of nomenclature, and an etiologic classification of all types of pulmonary hypertension.