Since intracellular Na+ activity (aiNa) is one important determinant of Na+ K(+)-pump rate as well as excitability and the finely tuned contractility, it is surprising that the relation between aNa and pump rate reported by different authors has kQ5 varying between 10 and 40 mmol L-1. Other data also point to a variable relation between pump rate and aiNa. During stimulation of isolated rat soleus muscles at 2 Hz, ouabain-sensitive 86Rb uptake was increased in spite of the intracellular Na+ remaining unaltered. In isolated cardiomyocytes, a transient Na+. K(+)-pump current was observed upon activation by extracellular K+ in spite of good control of aiNa. Na(+)-loaded, isolated, sheep cardiac Purkinje fibres initially hyperpolarized over a period of up to 1 min upon activation of the Na+, K+ pump with no detectable change of aiNa. These examples are compatible with the existence of a micro-environment close to the membrane where diffusion is slower than in the rest of the cytosol, so that local aiNa may fluctuate or gradients may develop as visualized by Wendt-Gallitelli at al. (1993). We conclude that the reported relationships between Na+, K+, pump rate and aiNa in intact cells probably underestimate the true affinity of the Na+, K+ pump for Na+ due to a functional diffusion barrier beneath the sarcolemma, and also because of incomplete cell dialysis in whole-cell voltage clamp experiments. The Na+, K+ pump seems to be preferentially supplied with Na+ from the outside through neighbouring channels and transporters.