The human aquaporins,AQP3,AQP7, AQP8,AQP9, and possibly AQP10, are permeable to ammonia, and AQP7, AQP9, and possibly AQP3, are permeable to urea. In humans, these aquaporins supplement the ammonia transport of the Rhesus (Rh) proteins and the urea transporters (UTs). The mechanism by which ammonium is transported by aquaporins is not fully resolved. A comparison of transport equations, models, and experimental data shows that ammonia is transported in its neutral form, NH(3). In the presence of NH(3), the aquaporin stimulates H(+) transport. Consequently, this transport of H(+) is only significant at alkaline pH. It is debated whether the H(+) ion passes via the aquaporin or by some external route; the investigation of this problem requires the aquaporin-expressing cell to be voltage-clamped. The ammonia-permeable aquaporins differ from other aquaporins by having a less restrictive aromatic/arginine region, and an exclusively water-permeable aquaporin can be transformed into an ammonia-permeable aquaporin by single point mutations in this region. The ammonia-permeable aquaporins fall into two groups: those that are permeable (AQP3, 7, 9, 10) and those that are impermeable (AQP8) to glycerol. The two groups differ in the amino acid composition of their aromatic/arginine regions. The location of the ammonia-permeable aquaporins in the body parallels that of the Rh proteins. This applies to erythrocytes and to cells associated with nitrogen homeostasis and high rates of anabolism. In the liver, AQPs 8 and 9 are found together with Rh proteins in cells exposed to portal blood coming from the intestine. In the kidney, AQP3 might participate in the excretion of NH(4) (+) in the collecting duct. The interplay between the ammonia-permeable aquaporins and the other types of ammonia- and urea-permeable proteins is not well understood.