We describe a method for measuring plasma, erythrocyte, and leukocyte sodium (Na+), potassium (K+), and magnesium (Mg2+) concentrations in 10-mL blood specimens. After separating cells with Ficoll-Hypaque and washing with isotonic choline chloride, erythrocytes and leukocytes are counted, so that results can be expressed as amount of substance per cell and also to monitor cell integrity and possible contamination. Plasma and cell lysates were analyzed (CV less than or equal to 7.0%) with flame photometry and atomic absorption spectrometry. Reference intervals for an elderly population with values for plasma electrolytes within reference intervals are similar to those for younger healthy subjects. From data on biological variation, reference values for erythrocyte cations are not of much use, and analytical goals for precision are not met, but the results might be useful for monitoring disease progression in individual patients. In contrast, reference values for leukocyte cations are theoretically of use and goals are achieved, but large changes are required before consecutive results can confidently be said to be significantly different.