1. The effects of a number of amino acids, peptides and disaccharides on the potential difference across the wall of the rat small intestine have been studied.2. All the L-amino acids tested, except lysine and arginine, and the three D-amino acids tested stimulate the potential when present in the mucosal fluid.3. The concentration dependence and time course of the potential differs between different amino acids.4. The results suggest a close correlation between the active transport of an amino acid and the potential change which it evokes.5. Glycyl-glycine, glycyl-L-alanine and tri-glycine stimulate the potential and this appears to be due to the amino acids liberated by hydrolysis.6. Maltose and sucrose, but not lactose, stimulate the potential, and the effect appears to depend on the extent of hydrolysis of the disaccharide.7. The magnitude of the potential varies in different parts of the intestine. For the amino acids tested the maximum potential occurred in the distal ileum, while in the case of hexoses the maximum potential was found in the mid-intestine.8. The results are discussed in relation to the mechanisms of transfer of hexoses and amino acids.