Using a rate-dialysis technique at 0-2 degrees C, the affinities of Na+ and K+ for the sodium pump of pig kidney outer medulla were determined from their effects on the binding of ADP to the enzyme. Since all experiments were carried out in the presence of Tris, the enzyme in absence of its specific ligands was assumed to be in a 'sodium-like' conformation. The model used in the analysis of the results assumed the enzyme to be a dimeric structure with two identical high-affinity nucleotide-binding sites. It is concluded from the data that the effects of Na+ and K+ on the binding of nucleotide to either subunit of a nucleotide-free enzyme are identical. The two subunits, taken together, have five identical and non-interacting K+-binding sites (Kdiss = 0.5 mM) whose occupation antagonizes nucleotide binding. The binding of a nucleotide molecule to a nucleotide-free enzyme results in the abolition of K+ binding to two of the five K+-binding sites. The binding of the second molecule of nucleotide prevents the binding of three more K+ ions to the enzyme. These results can explain the K+-induced curvature observed in nucleotide-binding isotherms in Scatchard plots. The two subunits, taken together, have five identical and non-interacting Na+-binding sites (Kdiss = 0.5 mM) whose occupation antagonizes the effects of K+ on nucleotide binding, but does not affect nucleotide binding directly. A few experiments carried out at 18 degrees C indicate that the model applies also at this temperature. It is likely that the cation sites investigated are intracellular ones and it is concluded that the binding of each cation to its site induces a specific conformational change in the neighbourhood of the site itself without affecting the regions around the remaining cation binding sites.