I n 1945, Homer W. Smith published an article in the JCI that clearly demonstrated that para-aminohippuric acid is the most suitable agent for the evaluation of renal plasma flow in both humans and dogs; in addition, the paper provided detailed methodology that is still in use today. This paper is but one of many outstanding works performed by Smith and his colleagues that clearly established the clearance technique as a powerful noninvasive approach to gain mechanistic insights into intrarenal function.