An ion-selective electrode incorporating valinomycin in a poly(vinyl chloride) membrane was used for examining potassium in blood and plasma. Using an electrode cell thermostated at 37 °C and a saturated potassium chloride liquid junction, the activity of plasma potassium appeared to be very similar to that for similar concentrations of potassium in physiological saline. An apparent difference in potassium activities between the plasma of whole blood and separated plasma was found to be comparable to the discrepancy between the pH of whole blood and plasma, and was attributed to an effect of red blood cells on the liquid junction of the measuring cell. The magnitude of the liquid junction potential between a bridge solution and blood is a major uncertainty both in the determination of activities of ions by electrode measurements (e.g., the biological pH scale) and in the measurement of potential differences across biological membranes. The advent of the highly selective plastic membrane electrodes enables this problem to be re-examined.