We previously described in red blood cells (RBCs) from uremic patients on dialysis a reduction in sodium (Na) efflux through the Na, potassium (K) cotransport system (Na,K CoT) while Na efflux through the Na,K pump was normal. We then examined Na efflux in fresh cells and in cells loaded to obtain one level of intracellular sodium (Nai) concentration at about 25 mmol/liter cell. In the present study we used similar cation flux methodology to examine the kinetics of cation efflux through the Na,K pump and Na,K CoT in uremic patients on dialysis. RBCs were Na-loaded to attain five different levels of Nai concentration over a range of 5 to 50 mmol/liter cells using the ionophore nystatin. At each level of Na-loading, the Nai achieved was similar in RBCs from controls and patients. Ouabain-sensitive Na efflux through the Na,K pump showed no difference in rate between normals and dialysis patients. When the kinetic parameters of this transport pathway were considered, the apparent affinity (K0.5) for sodium was not significantly different between controls and patients (18.4 +/- 2.3 vs. 20.0 +/- 2.6 mmol/liter cell) and the maximal velocity of efflux (Vmax) was also not different between controls and patients (9.6 +/- 0.7 vs. 8.5 +/- 1.2 mmol/liter cell/hr). Comparison of Nai-activated Na versus K efflux rates through the Na,K CoT in normal subjects demonstrated similar saturation kinetics, (K0.5 15.8 +/- 3.3 vs. 12.2 +/- 2.8 mmol/liter cell, Vmax 0.81 +/- 0.1 vs. 0.78 +/- 0.1 mmol/liter cell/hr) consistent with the known stoichiometric ratio of 1 Na:1 K:2 Cl described for this mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)