Epithelia are tissues consisting of sheets of similar cells bound closely together, which include the epidermis, the surfaces of the eyes, the surfaces of the hollow tubes and sacs that make up the digestive, respiratory, reproductive, and urinary tracts, and the secretory cells and ducts of various glands. Depending on their predominant function, epithelia can be described further as barrier, secretory, or absorptive, but often all three functions coexist. These are the tissues most exposed to environmental bacteria. The importance of epithelia in host defense is best illustrated by the common experience that disruption of the epithelial layers, such as occurs in a minor skin scrape or a burn, greatly increases the likelihood of penetrating infection. Mechanical barrier properties of epithelia, the physical cleansing effects of their secretions, and the shedding of colonized cells normally contribute to protection from microbes (1). Moreover, injured or infected epithelial cells help initiate the inflammatory response by emitting chemotactic signals that attract blood-borne host defense cells. Although the ability of various glands to produce antimicrobial substances has been appreciated since Alexander Fleming’s (2) pioneering studies of lysozyme in tears, respiratory secretions, and saliva, more recently it has become clear that barrier and absorptive epithelia also produce numerous antimicrobial substances (3–5). There are impressive similarities between the polypeptide arsenal of various epithelial cells and the prototypical professional host defense cells, the polymorphonuclear leukocytes. In some cases (eg, lysozyme and lactoferrin), the same genes are highly expressed in both cell types; in other cases (eg, defensins, peroxidase), the two cell types express different members of the same gene family. These similarities reinforce the notion that epithelial cells, like polymorphonuclear leukocytes, are important effectors of innate immunity.