The permeability of spherical lipid bilayer membranes (Pagano &, Thompson, 1967a,b) to sodium and chloride has been determined by direct measurement of isotopic fluxes and by calculation from the electrical parameters of this system. These membranes were generated in an aqueous sucrose density-gradient which was 0.2 m in NaCl, and were formed from a solution of egg phosphatidyl choline and n-tetradecane in chloroform-methanol. Using 22Na and 36Cl, the unidirectional fluxes MNa and MCl were found to be respectively 0.39 ± 0.02 and 90.2 ± 0.8 μμmoles/cm2/sec at 30°C °C, giving a value of MNa MCl = 0.0043. A plot of ln MCl versus T-1 was linear over the temperature range 10 to 30 °C, and yielded a value of 10.7 ± 0.4 kcal./mole for the activation energy for chloride permeation. The corresponding activation energy for sodium was not determined. Following the treatment of Hodgkin (Hodgkin, 1951), values of less than 2.0 μμmoles/cm2/sec for these fluxes were calculated from the electrical conductance and transference number data for this system. On the basis of the electrical transference data, the ratio MNa MCl was expected to be about 4.9. The isotopic chloride flux was examined in detail and shown to exhibit saturation kinetics. The difference between this flux and the value calculated from the electrical parameters may thus be accounted for by assuming the existence of an auxiliary carrier-mediated diffusion mechanism for chloride permeation. © 1968.