To evaluate the role of plasma tonicity in the postdialysis increment of plasma potassium (p[K(+)]), the outcome of two hemodiafiltration treatments that differed only in the Na(+) level in dialysate (Na(D))-143 mmol/L (high dialysate sodium concentration [H-Na(D)]) and 138 mmol/L (low dialysate sodium concentration [L-Na(D)])-were compared in the same group of uremic patients from the end of treatment (T0) to the subsequent 30 to 120 min and up to 68 h. Kt/V and intradialytic K(+) removal were comparable. At T0, plasma [Na(+)] was 145+/-1 and 137+/-1 mmol/L after H-Na(D) and L-Na(D), respectively (P<0.001). The difference in plasma tonicity persisted from T0 to T68 h. At T120, p[K(+)] was increased from the T0 value of 3.7+/-0.2 to 4.7+/-0.2 mmol/L (P<0.05) after H-Na(D), whereas it was unchanged after L-Na(D). The change of p[K(+)] was still different after 68 h (+76+/-10% and +50+/-7% in H-Na(D) and L-Na(D), respectively; P<0.05). Of note, in the first 2 h after the end of treatment, bioimpedance analysis revealed only in H-Na(D) a significant 11+/-3% decrement of phase angle that is compatible with a decrease of intracellular fluid volume at the expense of the extracellular volume. Similarly, within the same time frame, in H-Na(D), a significant reduction of mean corpuscular volume of red cells, associated with a 2 +/-1% decrease of the intracellular [K(+)], was observed. In contrast, mean corpuscular volume of red cells did not change and erythrocyte [K(+)] increased by 6+/-1% after L-Na(D) (P<0.005 versus H-Na(D)). Thus, hypertonicity significantly contributes to the increase of p[K(+)] throughout the whole interdialytic period by determining intracellular fluid volume/extracellular volume redistribution of water and K(+).