Abnormalities of membrane sodium transport are one of the manifestations of chronic renal failure. Following correction of the renal failure by renal transplantation erythrocyte membrane NaK ATPase activity increases to supranormal values. In the present study, direct measurements of erythrocyte sodium efflux were performed in 21 renal transplant patients. The mean rate constant for total sodium efflux was increased from 0.40 ± 0.01 in a group of control subjects to 0.45 ± 0.02 in the transplant patients (p < 0.02). This increase in the total sodium efflux rate constant was attributable to an increase in the glycoside sensitive component of sodium efflux which averaged 0.26 ± 0.01 in the control subjects, compared to 0.32 ± 0.02 in the transplant patients (p < 0.01). Intracellular sodium was significantly lower in the patients (5.8 ± 0.3 mmol/l of erythrocytes) than it was in the controls (7.5 ± 0.2 mmol/l of erythrocytes). Overall pump flux was not increased in the renal transplant patients, suggesting that a new steady state had been established in their erythrocytes, with the red cell sodium set at a new level. When normal erythrocytes were preincubated with the plasma of renal transplant patients, all components of sodium efflux remained normal. The plasma of renal transplant patients also was ineffective in inducing a change in cell membrane NaK ATPase activity in vitro. It is concluded that following renal transplantation there are changes in erythrocyte sodium transport, which are the obverse of those seen in uremia. Although further studies will be necessary before a pharmacologic explanation for these changes can be ruled out, it is possible that they represent overcompensation in a transport system previously exposed to prolonged uremic suppression.