Several plant protein inhibitors of hydrolytic enzymes have been widely investigated with the aim to evaluate their potential biotechnological use in agriculture. These proteins, when expressed in transformed plants, could confere resistance to a number of insect pests by interferring with their digestive processes. Three monomeric proteins, inhibitors of proteolytic enzymes, have been isolated from endosperm of Triticum aestivum; these inhibitors were fully sequenced and extensively characterized in our laboratory. Two of these, coded WSCI and WCI, are capable to inhibit pancreatic chymotrypsins as well as chymotrypsin-like activities present in the digestive apparatus of some insect larvae (i.e: Tenebrio molitor, Plodia interpunctella, Helicoverpa armigera). The third inhibitor, named WTI, in addition to pancreatic trypsins is able to interfere with a number of trypsin-like activities isolated from the midgut of insects attacking crops in open field and stored cereals. At the moment, our group is involved in researches whose final aim is to explore the potential biotechnological use of these inhibitors in trasforming plants of agronomic or ornamental interest. However, since by several authors has been pointed out the role played by a number of cereal proteins in some human allergenic pathologies, we are also interested in evaluating the potential risks associated with the ingestion of: i) foods prepared with wheat over-espressing proteinase inhibitors; ii) foodstuffs derived from plants transformed with the wheat inhibitor’s cDNAs. Our activity can be described with four distint (but strictly correlated) research lines. A. Structural and biochemical studies on wheat protein inhibitors of serine proteinases: physiological roles and potentialities. B. cDNA cloning and heterologous expression of wheat proteinase inhibitors: production of multi-functional chimeric molecules. C. Studies aimed to evaluate toxicity and allergenicity of the wheat inhibitors both as whole molecules and after proteolytic treatments simulating the physiological process of digestion. D. Use of cDNAs encoding wheat protein inhibitors (also in combination with other insect control-genes) with the aim to obtain plants, of agronomic or ornamental interest, with enhanced defensive properties against pest’s attack.