The determinants of weak electrolyte influx into everted segments of rat small intestine have been studied. Preliminary experiments showed that the observed influxes could be described as unidirectional, diffusional fluxes of the nonionized compound uncomplicated by a parallel ionic component. It is shown that the determinants of weak electrolyte influx in this situation may be described in terms of the resistance of the unstirred layer to movement from the bulk phase to the cell surface, the degree of ionization of the weak electrolyte at the cell surface, and the cellular permeability to the nonionized weak electrolyte. Quantitative considerations indicated that the unstirred layer was totally rate-limiting in the cases of some poorly ionized, or highly permeant compounds, but the unstirred layer was not totally rate limiting for most of the compounds studied. Calculation of cellular permeabilities for the nonionized forms of weak electrolytes required assumptions to be made concerning the pH value in the surface fluid layer. A uniform set of permeability data including both weak acids and weak bases was obtained only when it was assumed that the pH in the surface fluid layer was equal to that in the bulk phase, and it was concluded that these studies do not support the concept of a microclimate of distinctive pH at the epithelial surface as a determinant of weak electrolyte transport.
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