The path leading to the discovery and development of the first angiotensin- converting enzyme (ACE) inhibitor, captopril, as a valuable agent in the management of cardiovascular disease provides a typical example of the complexities and uncertainties that surround novel drug research. The trail starts in 1898 with Tigerstedt’s1 discovery of the pressor effects of a renal extract, renin, which was able to constrict resistance vessels in the arterial tree without altering cardiac output. He subsequently showed that renal extracts caused a marked pressor effect in nephrectomized animals. However, other investigators in the field were unable to repeat his observations, and so he abandoned studies on the action of renin. The reason for the failure to replicate Tigerstedt's experiments is probably that the renin in the extracts of other investigators was easily destroyed by keeping it at room temperature with or without the additional effects of bacterial contamination...