Because of the countercurrent multiplier system, there is a strong gradient for water reabsorption from the collecting duct that increases in strength toward the papillae. Because water reabsorption is a passive process, the maximum achievable urine concentration is equal to the peak osmolality in the medullary interstitium, about 1200 mOsm/kg H₂O. Such concentrations are only achievable in long-looped nephrons, however, because short-looped nephrons do not reach the inner medulla.

In addition to its direct effects on aquaporin channels, ADH has several actions that enhance the countercurrent system and thus increase the gradient for water reabsorption. In particular, this hormone increases solute reabsorption from the thick ascending limb, constricts vasa recta capillaries to reduce solute washout, and increases urea reabsorption from the inner medullary collecting duct. Some of the urea that drifts toward the cortex is secreted back into more proximal segments of the renal tubules so that it can be deposited again in the inner medulla.

In response to decreases in plasma osmolality, ADH release is inhibited, and AQP-2 channels are consequently endocytosed. The lack of water reabsorption from the collecting duct, coupled with the ongoing reabsorption of sodium from this segment, dilutes the urine to a minimum osmolality of 50 mOsm/kg H₂O.

Over the course of several hours, variable input from the ADH system leads to accumulation of urine in the bladder that has an osmolality between 50 and 1200 mOsm/kg H₂O. In patients with abnormal serum sodium concentrations, measurement of the urine osmolality can indicate whether the defect lies in the urine concentration process or elsewhere.