Antimicrobial proteins stored in lysosome-like granules of neutrophils and macrophages probably play an important role in killing phagocytosed microbes after delivery to the phagolysosome. Among the granules' antimicrobial armamentarium are defensins, peptides that kill a broad spectrum of microorganisms in vitro. Antimicrobial defensins were recently also isolated from non-phagocytic granulocytes of the mouse small intestinal epithelium, from where they are secreted into the lumen to function extracellularly. Clarification of the antimicrobial mechanisms of defensins in intracellular and extracellular environments will provide a key to understanding peptide-mediated host defence.