In thinking about cytoprotection five questions seem pertinent: (i) what is 'cytoprotection'? For convenience I shall use this term in spite of the semantic controversies between certain centers. (ii) How does cytoprotection occur? In other words what are the mechanisms that impart protection to the surface epithelial cells of the stomach and duodenum? (iii) What agents can produce mucosal protection? (iv) Can cytoprotection be demonstrated in humans? (v) What does the future hold for protecting the upper gastrointestinal tract from damage? A satisfactory working definition is the ability of an agent (be it a drug, a hormone, etc.) at nonantisecretory doses to prevent mucosal damage produced by noxious agents. There are several potential mechanisms whereby prostaglandins as well as other agents can produce protection of the mucosa of the upper gastrointestinal tract. Prostaglandins stimulate mucus production and/or alteration of its constituents (1). Prostaglandins are potent stimulants of surface epithelial bicarbonate secretion and alter the pH-mucus barrier (2). Prostaglandins as well as other agents may protect mucosal damage by their intrinsic effect on mucosal blood flow (3). For example, prostacyclin is an extremely potent vasodilator whereas PGF2~ decreases mucosal blood flow while still affording mucosal protection. Protective drugs may produce alterations of cell membrane integrity (4). Furthermore, they may stimulate mucosal growth (C. Johansson, personal communication). In addition, prostaglandins may also maintain mucosal sulphydryls as described by Szabo and colleagues (5). Finally they may stabilize the tissue lysozymes