Background: Matrix metalloproteinase-7 (MMP7) processes mouse pro-␣-defensins to bactericidal forms in Paneth cells, and MMP7(Ϫ/Ϫ) mice are considered to be ␣-defensin-null. Results: Activated ␣-defensins occur in the colonic lumen of MMP7(Ϫ/Ϫ) mice. Conclusion: ␣-Defensins are activated in MMP7(Ϫ/Ϫ) large bowel lumen by alternative proteolytic conversion mechanisms. Significance: MMP7(Ϫ/Ϫ) mice are unsuitable for studying ␣-defensin deficiency in large intestine.