Sodium concentrations in erythrocytes are lower in women during the luteal phase of the menstrual cycle than in women studied during the follicular phase and in men. Sodium cotransport activity is lower in women during the follicular phase than in men. Women taking oral contraceptives show no monthly variations in erythrocyte sodium concentrations. Subjects with a family history of essential hypertension have higher sodium concentrations in erythrocytes than those with a different family background, partly because of reduction in sodium cotransport activity. Negroes have marked erythrocyte sodium accumulation due to lower activity of the sodium-potassium pump and cotransport system; they also have reduced sodium-lithium counter-transport. There is no difference between negroes with or without haemoglobin S. There are no changes in erythrocyte potassium concentrations in relation to sex, menstrual phase, race, familial essential hypertension, presence of haemoglobin S or use of oral contraceptives. These physiological variations indicate the factors which must be standardized to study sodium concentrations in cells and sodium transmembrane flux.