The importance of the hydrophobic nature of the membrane in certain functions of the intestinal epithelium was investigated by determining the variations in short-circuit current (Isc), potential difference (PD), and conductance (G) in rat ileum in the presence of the first eight alcohols in the n-aliphatic series. At the lowest alcohol concentrations and in the presence of Ringer-galactose, there was transitory stimulation of Isc and PD that did not occur in the presence of theophylline or in the absence of chloride. With or without theophylline all the alcohols tested inhibited Isc and PD and slightly increased G as a function of their concentration. The modifications in Isc were attributed to the inhibition of active sodium transport. These results demonstrate a linear relation between the logarithm of the concentrations causing 50% inhibition of Isc and the chain length of the alcohols. The variations in free energy required to transfer one -CH2- to the site at which the alcohols exert their activity were, respectively, -582 and -589 cal in the presence and absence of theophylline. These values show that the observed modifications in free energy are due to solubilization of the alcohols in a very hydrophobic zone of the tissue, confirming that the functional activities measured are dependent on the hydrophobicity of the membrane.