AbstractLocal tissue fluid within the subcutaneous tissues of the hind legs of dogs was sampled with a liquid paraffin cavity method. The potassium and sodium concentrations of nanoliter samples of the tissue fluid were analyzed with an ultra‐micro flame photometric method and compared to the plasma concentrations of these ions. The average potassium concentration in the tissue fluid was 4.67 meq/l and the average sodium concentration was 153.4 meq/l; the corresponding plasma values were 3.78 meq/l and 142.3 meq/l respectively. The average individual potassium tissue fluid: plasma ratio was 1.25 (P<0.001 vs. 1.0) and the sodium tissue fluid: plasma ratio 1.08 (P<0.001 vs. 1.0). Possible sources of error at sampling and analyses have been evaluated. The potassium and sodium content of the local tissue fluid was higher than expected of an ultrafiltrate of plasma according to the generally accepted Gibbs‐Donnan constant (0.96) for these ions. The apparent deviation of the obtained values from the Gibbs‐Donnan constant can be explained by assuming that charged anionic macromolecules in the ground substance of the tissues affect the cation distribution in the local tissue