After the development of blood pressure measurements in humans, the association of high blood pressure with renal disease was established. Injection of extracts of various organs in an attempt to replace their secretions was common in the 19th century, and it was therefore natural for Tigerstedt and Bergman to investigate the effects of renal extracts. In this way, they discovered renin. This paper covers the methods by which its mode of action was uncovered, as well as its relation to renal ischemia and hypertension.