The relationships between currents generated by the rabbit Na+/glucose cotransporter (SGLT1) and the fluxes of Na+ and sugar were investigated using Xenopus laevis oocytes expressing SGLT1. In individual voltage-clamped oocytes we measured: (i) the current evoked by 10 mM alpha MG and the 22Na+ uptake at 10 mM Na+; (ii) the currents evoked by 50 to 500 microM [14C]alpha MG and the [14C]alpha MG uptakes at 100 mM Na+; and (iii) phlorizin-sensitive leak currents in the absence of sugar and 22Na+ uptakes at 10 mM Na+. We demonstrate that the SGLT1 leak currents are Na+ currents, and that the sugar-evoked currents are directly proportional to both alpha MG and Na+ uptakes. The Na+/alpha MG coupling coefficients were estimated to be 1.6 at -70 mV and 1.9 at -110 mV. This suggests that the rabbit SGLT1 Na+/alpha MG stoichiometry for sugar uptake is 2 under fully saturating, zero-trans conditions. Coupling coefficients of less than 2 are expected under nonsaturating conditions due to uncoupled Na+ fluxes (slippage). The similarity between the Na+ Hill coefficients and the coupling coefficients suggests strong cooperativity between the two Na+ binding sites.