Summary. The operation of the multicompartmental frog skin epidermal model 10E described in the preceding paper was tested to find out by computer simulation whether it responds to changes in [Na +] in the same manner as frog skin. In the range from 5 to 115 mra [Na+]o, the rate of net Na + flux across skin is known to increase. The results can be fitted to Michaelis-Menten's law of reaction kinetics, or, alternately, to Hoshiko's linear function, plotting flux vs. log [Na+]o . Model 10E simulated the laboratory results on skin, provided that the rate coefficients at the site of entry of Na + into the system were varied in exactly the same manner as they actually were found to vary in skin. In model studies, Na + backflux (outflux) decreased with increasing [Na+]o, contrary to observations on skin. This discrepancy may be related to adaptive reactions in skins (decrease in permeability) when [Na+]o is lowered, a feature that has not been modeled. It is known that the skin p.d. changes, mostly, by approximately 35 mV per decade change in [Na+]0 . Model 10E gave very nearly the same result when the rate coefficients for entry of Na + were changed as mentioned above (i.e., varied exactly as they were found to vary in skin). Skin and model 10E behaved similarly in that, at [Na+]0 = [Na+]i = 115 mM, the extent to which labeling with Na* from the outside (12%) and from the inside (88%) is possible was the same. Model data are presented which show in which way the Na + pools, [Na +] in the individual compartments, and intercompartmental fluxes changed with changing [Na+]o . Because of lack of experimental data on skin for comparison, these calculated results are purely hypothetical, but they are not unreasonable.When isolated frog skin is mounted between two oxygenated frog Ringer's solutions, one observes a net transport of NaC1 in the direction from the epidermis to the corium [9]. This results from an active inward transport of Na +, with C1-following passively [23]. The rate of net Na + transport (J~") is approximately 1 gEquiv x cm-2 x hr-1. When the [Na + ] on the epidermal side (outside) is lowered, the rate of active inward Na § transport and of 3~ a is found decreased [3,22]. A plot of J~" vs.[Na+]o suggests saturation kinetics of the active Na + transport process. The 5*