Like other regional circulations, the medullary circulation supplies oxygen and other primary substrates to the medulla and removes carbon dioxide and other waste metabolites. It also acts as a countercurrent exchanger and simultaneously removes water reabsorbed from the renal tubule to preserve mass balance. Our present understanding of how the medulla serves both these functions at the same time is illustrated in Figure 3. Blood leaves the efferent arteriole with an elevated plasma protein concentration as a consequence of glomerular filtration, and flows down descending vasa recta within a vascular bundle. The increased interstitial osmotic-concentration coupled with a finite capillary reflection coefficient for small solutes causes additional water to be extracted so that at the termination of descending vasa recta, the plasma protein concentration exceeds that in the systemic circulation by approximately twofold. Solute, urea more than sodium chloride, also enters descending vasa recta. As blood flows through the interconnecting capillary plexus and up ascending vasa recta, transcapillary oncotic and osmotic pressure differences combine to cause capillary uptake of fluid. There is also simultaneous loss of urea such that the medullary trapping of urea is very effective. Countercurrent exchange of sodium chloride, however, appears to be less efficient and as a consequence, not only water but sodium chloride is removed from the medulla. Antidiuretic hormone reduces medullary blood flow, both directly by its vasoconstrictor (V1-receptor mediated) effect and indirectly by its antidiuretic (V2-receptor mediated) effects. Prostaglandins are able to enhance medullary blood flow by counteracting vasoconstrictive influences.(ABSTRACT TRUNCATED AT 250 WORDS)