Various mechanisms to fend off microbial invaders have been devised by all living organisms, including microorganisms themselves. The most sophisticated of these mechanisms relies on the synthesis of immunoglobulins directed against specific microbial targets. However, immunoglobulin-based immunity operates only in a relatively minor subset of living species, namely the higher vertebrates. A much more ancient and widespread defense strategy involves the production of small peptides that exert antimicrobial properties. As products of single genes, antimicrobial peptides can be synthesized in a swift and flexible way, and because of their small size they can be produced by the host with a minimal input of energy and biomass. Wellknown examples of antimicrobial peptides are the cecropins that accumulate in the hemolymph of many invertebrates in response to injury or infection (reviewed by Boman and Hultmark, 1987) and the magainins that are secreted by glands in the skin of amphibians (reviewed by Bevins and Zasloff, 1990). Cecropins and magainins are small (20-40 residues) basic peptides displaying an amphipathic a-helical structure that can integrate in microbial membranes to form ion channels (Duclohier, 1994). Another class of antimicrobial peptides is formed by the Cys-rich peptides, which in contrast to cecropins and magainins, have a complex cystine-stabilized three-dimensional folding pattern often involving antiparallel ,3-sheets. Defensins are one class among the numerous types of Cys-rich antimicrobial peptides, which differ in length, number of cystine, bonds, or folding pattern (reviewed by Boman, 1995). Insect (34-43 residues, three disulfide bridges) are, like cecropins, produced in a pathogeninducible manner by the insect fat body and secreted in the hemolymph (reviewed by Hoffmann and Hetru, 1992). Mammalian (29-34 amino acids, three disulfide bridges) are produced by various specialized cells in the mammalian body (reviewed by Lehrer et al., 1993; Ganz and Lehrer, 1994). For example, they are very abundant in granules of phagocytic blood cells. These granules fuse with phagocytosis vesicles containing microorganisms, where the are thought to contribute, together with other antimicrobial proteins and active oxygen species, to killing of the engulfed microorganisms. Defensins are also secreted by epithelial cells of the intestines and airways, where they may help maintain the normal microbial flora in a steady state. In addition, the expression of in the airway epithelium has been shown to be up-regulated after exposure to bacterial lipopolysaccharides (Diamond et al., 1993). The importance of in innate immunity of humans is underscored by the observation that certain disorders characterized by recurrent infections are associated with a lack of in blood phagocytes (Ganz et al., 1988). Moreover, transposon mutants of a pathogenic Salmonella strain known to infect and grow inside phagocytes simultaneously lost their resistance to (and other antimicrobial peptides) and their virulence (Groisman et al., 1992). Recently, we characterized a novel class of peptides whose structural and functional properties resemble those of insect and mammalian defensins. Hence, we termed this family of peptides plant defensins (Terras et al., 1995).