Quantification of physiologic defensin concentrations in vivo is complex, as defensins are present at high local concentrations within specific cell types or upon release from cells into confined anatomical niches (e.g., crypts of the small intestine) but can become diluted in extracellular fluids. For the myeloid -defensins, Daher et al. estimated ~3 mM (10 mg/ml) HNPs in neutrophils, with even higher local concentrations in the azurophilic granules in which they are stored 1 . For the enteric -defensins, Ayabe et al. estimated concentrations of ≥3.5 mM (15-100 mg/ml) in the crypt lumen, the site of Paneth cell degranulation 31 . These concentrations are likely similar in the human small intestine, where HD5 expression exceeds that of HD6 by 6-fold 32 . In healthy patients, epithelial lining fluid of the lung contains 31-79 nM HNP1-3, nasal fluid contains ~2.7 M HNP1-3, saliva contains 0.3-3 M HNP1-3, and vaginal secretions contain ~1.5 M HNPs and 0.3-14 M HD5 23; 33; 34; 35; 36; 37; 38 . For the -defensins, 5-10 nM HBD2 has been measured in nasal fluid 37; 39 . However, in certain disease states defensin levels can be highly elevated. For example, 57 M to 2.4 mM concentrations of HNP1 have been found in epithelial lining fluid of cystic fibrosis patients 36 . Overall, the concentrations of defensins present in vivo are generally within the range that is needed for direct antiviral activity by -defensins and generally below the concentrations required for direct antiviral activity by -defensins. Wilson et al. 