Recent DNA cloning studies have revealed the existence of a large family of homologous sugar transporters in both prokaryotic and eukaryotic organisms. The family includes passive transporters typical of mammalian tissues and active, H(+)-linked sugar transporters from bacteria. Each of these transporters characteristically contains two groups of six putative membrane-spanning alpha-helices separated by a large, hydrophilic, cytoplasmic region. Both the N-terminal and C-terminal regions of the sequence are also predicted to be cytoplasmic. Biophysical and other studies on the human erythrocyte glucose transporter, the only member of the family so far isolated in functional form, suggest that the membrane-spanning alpha-helices associate to form a hydrophilic channel or a substrate-binding cleft extending across the membrane. It is likely that the mechanism of substrate translocation involves alternate exposure of the substrate-binding site to each face of the membrane via a conformational change. Studies in progress on the erythrocyte transporter are beginning to identify regions of the protein involved in substrate binding and the conformational change, and should throw light on the mechanism of sugar translocation in the sugar transporter family as a whole.