Evidence for water channels in red blood cells is reviewed. In an entropically driven reaction, organic mercurials decrease water permeability, elevate the activation energy, and reduce the ratio of osmotic to diffusional water permeabilities to unity so that water transport properties of red blood cells are hardly distinguishable from lipid bilayers. It is concluded that mercurials close the water channels. A variety of kinetic, pharmacological, and comparative evidence converges on the conclusion that urea and other solutes are excluded from water channels. Urea apparently permeates the red cell membrane via a facilitated diffusion system, which plays an important role when red blood cells traverse the renal medulla; rapid urea transport helps preserve the osmotic stability and deformability of the cell, and it helps prevent dissipation of extracellular osmotic gradients. Water apparently traverses the channel via a single-file mechanism; the very low channel permeability of H+ is explained if the channel contains fixed charge, or alternatively, if the mobile water molecules within the channel do not form a continuum. An alternative unitary pore hypothesis for simultaneous transport of water, ions, and small solutes is also discussedl.