The proposed studies form part of a continuing investigation into the cellular mechanisms underlying the transport of water, ions, and water soluble non-electrolytes across the epithelial cell layer of the small intestine. Specifically, the investigation is concerned with the kinetics, energetics, and electrophysiology of ionic absorption and secretion by this tissue. Coupling between ionic transfer processes (e.g. sodium and chloride transport) and between these processes and the transport of certain organic solutes (e.g. sugars, amino-acids and oligopeptides) is also a major concern within the overall scope of the project. Experimental techniques employed include the measurement of transepithelial potential difference and short circuit current, and of the mucosal sodium and potassium concentrations, measurement of mucosal chloride concentration by electrometric titration, direct determination (with ion-selective microelectrodes) of intracellular sodium, potassium, and chloride activities, and measurement, by radiotracer techniques, of transepithelial and transmucosal fluxes of ions, sugars and amino-acids. Because of its exceptional stability in vitro and its functional resemblance to maximum small intestine, the isolated small intestine of the bullfrog is used as an experimental preparation. The overall goal of this investigation is to provide new experimental information and generate models of intestinal function which will be of use in the development of novel conceptual and technical approaches to the management of human disorders which stem from or involve malfunction of the small (e.g. carbohydrate malabsorption and conditions such as cystinuria and Hartnup disease where intestinal amino-acid transport defects parallel those observed in the kidney). In addition, this investigation is developing techniques (notably techniques for the measurement of intracellular ionic activities) which are already contributing significantly to the study of other transporting epithelia (e.g. renal tubular epithelium). Hopefully, these techniques will play a greatly increased role in future studies of epithelial physiology and pathophysiology.