The sodium and potassium concentrations of the red blood cells and plasma were investigated in 93 children with cardiac disease, most of them with congenital heart defect, and in 48 healthy children of the same age. The red blood cell sodium and potassium concentrations were constant within a narrow range in normal subjects, but varied profoundly in pathological conditions. Digitalis treatment caused RBC Na+ and plasma K+ levels to increase and the RBC K+ level to decrease by blocking the Na+-K+ pump. The highest RBC Na+ concentration was observed in critically ill patients with congestive heart failure treated with digoxin. An augmented RBC sodium value was found in heart malformations with left to right shunt and in congestive cardiomyopathy that was not treated, whereas in patients with right to left shunt lower RBC sodium, higher RBC potassium and plasma potassium values were registered without any treatment. In cases of hyperkinetic circulation without any congenital heart defect the value of RBC sodium was definitely low. A low sodium and a high potassium level of the RBC were found after total correcting heart surgery. It is concluded that measurement of changes in sodium and potassium concentrations of the red blood cells is not a reliable method for assessment of the efficacy of digitalis treatment. The results point to the accompanying phenomena at a cellular level in heart disease.