The effect of external Na+ concentration on p-aminohippurate uptake by isolated kidneys of newt (Triturus pyrrhogaster) was studied kinetically and electrophysiologically. 2. p-Aminohippurate uptake conformed to Michaelis-Menten type kinetics in regard to both p-aminohippurate and Na+ concentrations in the incubation medium. Kinetic studies revealed that reduction of Na+ concentration increased the values of Kt without altering the maximal rate (V) of p-aminohippurate uptake. The values of Kt were a linear function of the reciprocal of Na+ concentration. These results suggest the presence of interaction between p-aminohippurate and Na+ at the carrier level, i.e. Na+-coupled cotransport. 3. p-Aminohippurate had no effect on the electrical potential difference across the peritubular membrane in both 10 and 100 mM Na+ solutions, suggesting that p-aminohippurate is transported across the peritubular membrane in a form of electrically neutral carrier complex. This is consistent with the results of the kinetic studies. 4. p-Aminohippurate uptake was proportional to the electrochemical potential gradient of Na+ (delta mu Na) across the peritubular membrane. This result indicates that the maintenance of sufficient delta mu Na appears to be necessary for the accumulation of p-aminohippurate against its electrochemical potential gradient, supporting Na+ gradient hypothesis.