Cotransporters are membrane proteins which couple the downhill transport of cations (Na¤ or H¤) to the uphill transport of substrates (sugars, amino acids, neurotransmitters, vitamins and ions) into cells. In addition to the secondary active transport of solutes, many cotransporters exhibit a cationic leak current (uniporter mode), which is the passive transport of Na¤ (or H¤) in the absence of substrates (see Wright et al. 1996). We have previously suggested that cotransporters can function as passive (osmotic) and secondary active water transporters. For example, the Na¤glucose cotransporter SGLT1 exhibits an osmotic water permeability that is blocked by the inhibitor phlorizin (Zampighi et al. 1995;Loo et al. 1996;Loike et al. 1996;Meinild et al. 1998a). Under sugar-transporting conditions, SGLT1 transports 200-260 HµO molecules along with two sodium ions and one glucose molecule for every transport cycle. This solute-coupled water transport occurs in the absence of, and even against, an osmotic gradient (Loo et al. 1996;Zeuthen et al. 1997;Meinild et al. 1998a;Wright et al. 1998). Similar observations on the K¤-Cl¦, H¤lactate, Na¤-Cl¦-GABA, Na¤-iodide and H¤-amino acid transporters indicate that water transport may be a general phenomenon in this class of membrane transport proteins with coupling coefficients varying from 50 to 500 water molecules per substrate molecule (