We have shown that the unstirred water layers in the intestine are rate-limiting for the aborption of a variety of lipid molecules. In addition, it has been shown that the microvillus membrane of the mucosal cell is relatively polar. These findings will be extended in the proposed investigations in five general areas. First, while previous studies have defined the effective thickness and surface area of the unstirred water layer in the intestine with respect to diffusion-limited compounds, new studies are planned to delineate these parameters for passively absorbed solute molecules whole uptake is only partially limited by unstirred layers. Second, the passive permeability coefficients for a series of probe molecules will be measured across the cell membrane of nonepithelial cells such as the isolated adipocyte and liver cell and the muscle cell of the diaphragm. These permeability data will be analyzed in terms of incremental free energy changes associated with various substituent groups on the probe molecules. Third, since unstirred layers have been shown to profoundly influence the kinetic parameters of active transport, the theoretical equations for the kinetics of active transport in the presence of unstirred layers will be derived. Such equations must take into account the surface area and thickness of this diffusion barrier. Fifth, studies will be undertaken to determine experimentally the parameters of the unstirred layer so that these terms may be used in the appropriate equations. Sixth, if the equations and parameters for active transport can be determined then a systematic evaluation of the kinetic parameters of active transport of various sugars and amino acids will be undertaken. These studies should provide a more detailed and accurate appraisal of the overall effects of unstirred layers in the intestine on both passive and active transport processes and a comparison of the permeability characteristics of several other cell membranes in addition to the microvillus membrane.