Facilitative glucose transporters (GLUTs) have recently been shown to be multifunctional, transporting substrates other than sugars, such as water and ring compounds as large as nitrobenzene-diazol-aminoglucose. Other membrane proteins, including transporters and cystic fibrosis transmembrane conductance regulator, have also revealed a finite permeability to water. We compare the alpha-helical and beta-barrel models for the structure of GLUTs, discuss recent evidence, and argue that a beta-barrel fold explains it better. We show a model for GLUTs consisting of a relatively rigid beta-barrel translocation unit ("channel") of diameter ample enough to allow permeation of the above substrates (approximately 20 A) but gated shut by mobile loops at both ends. Such gates would open only after aromatic interactions would lead to binding of the ring substrates for GLUTs; water would, however, traverse crevices in the closed gates. Using the insights gained from GLUTs, we propose that other transporters may share with GLUTs the motif of a beta-barrel channel and would be permeable to water due to the presence of such channels together with similarly behaving gates.