It is generally accepted that cotransporters act as passive water channels but an active mode of transport has also been suggested. Transmembrane osmotic gradients induce passive water transport in cotransporters and in a cell the magnitude of these fluxes may be significant: both the number of cotransporters and the unit water permeability are high. For the Na+- glutamate cotransporter (EAAT1) the unit water permeability is one tenth of that of the water channel AQP1. In addition, it is gated by the presence of substrate and by the membrane potential (MacAulay et al., 2001;MacAulay et al., 2002). Similar properties have been observed for other cotransporters of the symport type, e.g. the K+ – Cl- (KCC4), the Na+ – K+ – Cl- (NKCC1), the H+-lactate (MCT1), and the Na+-glucose cotransporter (SGLT1), for a review see (Zeuthen & MacAulay, 2002b). During cotransport another component of water transport emerges in parallel and independently of the passive water transport. By this mechanism, water can move uphill against the osmotic gradient since the energy contained in the substrate gradients is transferred to the transport of water. In short, cotransporters act as molecular water pumps. We have investigated active water transport in intact tissues by ionselective microelectrodes and fluorescence methods as well as in Xenopus oocytes, in which relevant cotransporters were over-expressed. In general, the stoichiometry between the cotransport of water and the non-aqueous substrates is fixed for a given transporter irrespective of transport conditions. Coupling ratios of 150 to 500 water molecules per charge translocated by the protein has been determined for different cotransporters, which mean that the tonicity of the transportate may be compatible to that of the surrounding tissues. Cotransport of water has been demonstrated in symports, such as those mentioned above, but not in the antiports for Na+/H+ and Cl-/HCO3-. Given physiological values of intra- and extracellular diffusion coefficients, effects of unstirred layers can be ruled out (Zeuthen et al., 2002). For a recent review, see (Zeuthen & MacAulay, 2002a). The concept of molecular water pumps is relevant for a number of well-established physiological phenomena, which cannot be explained by simple osmosis. In the small intestine, water is transported uphill from the lumen into the blood; during digestive processes, the lumen can attain hyperosmolarities of more than 100 mosm l-1 relative to plasma (Reid, 1901). Glandular secretion also proceeds against an osmotic gradient; secretion of saliva, for example, can proceed against hydrostatic pressures of more than 2 meters of water (Ludwig, 1861). In brain, the synaptic cleft becomes hyperosmolar during neural activity (Dietzel et al., 1989); it is the role of neuroglia, in particular the astrocytes, to control the size and ion-concentrations of the extracellular space in the neuropil. Astrocytes are polarized with EAAT localized at the end facing the neuropil while the end abutting the blood circulation is rich in aquaporins, AQP4 (Nielsen et al., 1997). The water transport properties of EAAT suggest a new model for volume homeostasis of the extracellular space during neural activity.