Human beta -defensin-1 (HBD-1) was detected in breast milk in concentrations of similar to1 to 10 mug/mL. Breast tissue during lactation showed HBD-1 expression in mammary gland epithelia and within luminal secretions. The peptide demonstrated antimicrobial activity against Escherichia coli. HBD-1 may augment neonatal host defenses through antimicrobial effects or prime the adaptive immune system at mucosal surfaces.