The present invention employs an iterative application of BLAST and Hidden Markov Model (HMM) based searches which identified 34 .beta.-defensin genes in the human genome and 48 in the mouse genome. The present invention relates to novel antimicrobial peptides and derivatives thereof as well as the .beta.-defensin genes encoding the peptides. The invention further relates to methods of use of the peptides including a method of inhibiting microbial growth by administering an effective amount of the peptide alone or in combination with other antimicrobial agents or antibiotics.