The epithelium of the small and large intestine is, in fact, an outside surface of the body which separates the outside (the intestinal lumen) from the internal environment of the body. The actual anatomic surface area of the small intestine exceeds the size of a doubles' tennis court and has two seemingly conflicting tasks. The more familiar task of the intestine is to act as an efficient absorbing surface to internalize nutrients and fluids. The second task, which is less familiar, is to act as a barrier between the external and internal environments to prevent the entrance into the body of potentially harmful antigenic, toxic, or carcinogenic compounds. This latter function of the intestine is often referred to as the harrierfunction of the intestine (1). The numerous components that together form this barrier include the surface mucus layer, the absorptive brush border cell membrane of the enterocytes, the paracellular junctional areas, the epithelial and subepithelial immune defense mechanisms, and the intestinal lymph nodes. The liver and spleen reticuloendothelial cells act as a reserve system to filter or trap compounds that should not, but do, manage to penetrate the barrier.

The discussion will be limited to the consideration of only one component of the intestinal barrier-namely, the epithelial layer of the intestine. The epithelial layer forms the most superficial physical portion of the barrier of the intestine and is composed of two separate components. The first component is the brush border lipid cell membrane of the enterocytes, and the second one is the vast paracellular space surrounding the brush border surface of the enterocytes and their tight junctions. This latter term, tight junc-tion, is an unfortunate one because it implies the existence of a relatively impenetrable cement-like substance, much like the grout between tiles, which would prevent luminal compounds from entering through this area into the lamina propria of the intestine. In fact, the tight junction, far from being'tight', is an active and dynamic space between cells which opens or closes (2) and allows relatively large amounts of fluids, nutrients, and medium-sized compounds to enter through it (3) into the lamina propria of the intestine. Recent studies suggest that the paracellular space may be a major route for the absorption of water, water-soluble nutrients such as sugars and amino acids, and some electrolytes (4). The tight junction appears to open after the ingestion of food and to serve as a portal for the absorption of nutrients