PLUNC (palate, lung and nasal epithelium clone) is a small, secreted protein that is expressed in the oropharynx and upper airways of humans, mice and rats. We have described a family of at least 14 PLUNC genes localized on chromosome 20 (in humans), 2 (in mice) or 3 (in rats). These rapidly evolving proteins are structurally related to lipopolysaccharide-binding protein (LBP) and bactericidal/permeability-increasing protein (BPI). In the present analysis we comment on the comparative aspects of this protein family, which may function to protect epithelial surfaces from pathogenic micro-organisms.