Our intestinal mucosa, particularly that lining the large bowel and terminal ileum, is in constant contact with a resident microflora that is both luxuriant and complex: It consists of some 100 trillion discrete prokaryotic cells comprising an astonishing variety of Gram-positive and Gramnegative facultative aerobic and anaerobic organisms (1). Under normal circumstances, the presence of this vast biotic mass is useful and benign in that it helps prevent colonization of the bowel by pathogens and does not in itself evoke inflammatory immune responses (the normal mucosal immune system is tolerant of its many antigens). Nevertheless, this flora can also cause disease, because there is now good evidence that excessive mucosal immune responses to components of the microflora, either due to abnormal or impaired effector or regulatory (suppressor) cell activity of the host, is the prime cause of inflammatory bowel disease (IBD)(2). One way by which cells in the intestinal milieu may prevent this possible outcome is to apply a number of checks on the resident microflora that control its overall size and composition. On page 1126 of this issue, Cash et al.(3) characterize one such check—the ability of epithelial cells lining parts of the mucosa to produce RegIIIγ (regenerating islet 3 gamma), a C-type lectin with bactericidal properties. This substance may not only regulate the mix of intestinal organisms, but may also eliminate potential pathogens that cannot be controlled by the microflora alone. Production of RegIIIγ was previously shown to be up-regulated in mouse intestinal cells after induction of mucosal inflammation and in patients with IBD (4). Cash et al. found that it is the product of Paneth cells, secretory epithelial cells at the base of the intestinal crypts in the terminal part of the small intestine (see the figure). However, these cells may not be the only site of production because RegIIIγ is also produced in the large bowel, which lacks Paneth cells (4). In addition, they found that RegIIIγ and its human homolog, HIP/PAP, bind to a carbohydrate component of peptidoglycan, a proteoglycan in the bacterial coat of most bacteria, particularly Grampositive bacteria. The authors observed that such binding leads to bacterial killing, thus making RegIIIγone of a number of antibacterial (antimicrobial) substances produced by