The reabsorption of amino acids by the proximal tubule is remarkably efficient. Current evidence indicates that this process occurs by Na+-amino acid cotransport or symport. The energy for amino acid entry is derived from the chemical and voltage gradient for Na+ entry across the apical surface of the renal cell maintained by pumping Na+ out of the cell by Na+-K+-adenosine triphosphatase (ATPase) activity at the basolateral membrane. We chose the beta-amino acid taurine to study the anionic requirements as well as voltage- and pH-dependence of Na+-taurine symport into rat proximal tubule brush border membrane vesicles. Maximal uptake was found when Cl- or Br- were the anions. The addition of various ionophores (amiloride, carbonyl cyanide-n chlorophenyl-hydrazone, and valinomycin) under pH-equilibrated conditions did not change taurine entry into the vesicle. Hill equation analysis of the initial rate of taurine uptake into vesicles indicates that transport operates by means of a 2 Na+:1 Cl-:1 taurine-carrier complex. Because taurine is a zwitterion, this complex has a net positive charge. Its entry into the vesicle is favored by the imposition of an outwardly directed K+ gradient in the presence of valinomycin. The movement of a quaternary complex of this type across the apical surface of the proximal tubular cell would assure that the movement of both Cl- and the amino acid is energized by the Na+ gradient. Because most amino acids are zwitterions at physiologic pH this complex would be positively charged, favoring entry into the voltage negative renal cell interior.