SUMMARY Carbohydrates play a significant role in the human diet and the extent of their consumption directly impacts human health. In order to control carbohydrate consumption, it is critical to understand how the gustatory system responds to them. Recently, we reported that humans can taste glucose-based oligosaccharides and that their detection is independent of the known sweet receptor. Building upon these findings, this proposal seeks to establish the range of oligosaccharides that humans can taste and further to determine the structural characteristics of oligosaccharides that enable their perception by humans. This project has two overarching hypotheses: (1) that humans can taste a wide range of oligosaccharides, and (2) that taste detection depends on the molecular structures of oligosaccharides with respect to the types of monomer building blocks, chain length, position and number of glycosidic linkages, and terminal residues. These two hypotheses will be tested by using a range of naturally existing, well-defined oligosaccharides and selected derivatives. Two functionally different groups of oligosaccharides will be considered: (a) starch-derived digestible oligosaccharides that are primary sources of dietary energy and (b) non-starch oligosaccharides that are not digested by humans but are considered beneficial to health (e.g., prebiotics). Recognizing that commercially available oligosaccharides are heterogeneous “cocktails” with undefined profiles, we propose to purify or isolate target oligosaccharides. Accordingly, an important additional outcome of this project will be publically available protocols for the preparation of well-defined, natural and derivatized oligosaccharides for human testing. These compounds should prove to be valuable candidate ligands for future studies aimed at the molecular characterization of oligosaccharide receptor(s).