Na(+)-dependent transporters, such as the Na+/glucose cotransporter (SGLT1) have long been characterized as having an overwhelming preference for Na+ as the essential ion. We have applied electrophysiological measurements to analyze the ability of protons to transport glucose with a cloned transporter, SGLT1, expressed in Xenopus laevis oocytes. Our results show that protons can drive sugar transport through SGLT1 in the absence of Na+ with the following characteristics: 1) the affinity of SGLT1 for H+ is 3 orders of magnitude higher than its affinity for Na+ (3 microM versus 20 mM); 2) H+ supports a higher maximum transport than Na+, suggesting an alteration in rate-limiting processes; and 3) the cation determines the transporter's affinity for sugar (at Vm = -50 mV, the apparent affinity for alpha-methyl-D-glucoside is 0.2 mM in Na+ and 20 mM in H+). The similarity in the kinetics of H(+)- and Na(+)-dependent sugar transport suggests that the transport mechanism for SGLT1 does not depend on the driving ion.