NaCl-sensitive, cationic peptide that participates in the innate host defense of respiratory and other mucosal tissues. Increased levels of HBD2 have been measured in the airways during chronic inflammation and infection. The cytokines, interleukin-1 and TNF, upregulate HBD2 mRNA expression in vitro, thus contributing to the hypothesis that HBD2 is inducible under proinflammatory stimuli. Further, HBD2 may promote “adaptive immune responses” by recruitment of dendritic and T-cells through interaction with the chemokine receptor, CCR6. Therefore, we questioned whether HBD2 levels were increased in BAL after lung transplantation and may be related to the pathogenesis of BOS. Methods: We performed a preliminary cross-sectional study which assessed HBD2 and lysozyme concentrations by semiquantitative Western Blot analysis in BAL obtained with concurrent lung biopsies [TBB]. Subject groups included: (i) Pre-transplant [PRE; N 9], (ii) Nine LT recipients with normal TBB histology [NORMAL; N 22] and (iii) Six LT recipients with Bronchiolitis Obliterans Syndrome [BOS; N 8]. Results: HBD2 concentrations [Mean SE] were as follows, for PRE: 0.204 0.18, NORMAL: 0.082 0.06, and BOS: 1.27 0.43 ng/ml [p 0.001; Kruskal-Wallis ANOVA]. For lysozyme, BAL concentrations were for PRE: 119.9 90.9, NORMAL: 174.9 101.6, and BOS: 51.2 13.8 g/ml [p NS]. Conclusions: Similar to normal lungs, HBD2 was not typically present in allografts during periods of quiescence, however was increased during an airway inflammatory milieu such as BOS. We speculate that elaboration of inflammatory cytokines during such conditions as allograft infection, may induce expression of HBD2 by respiratory epithelium and, via complex interactions with dendritic cells, promote the development of BOS. Further, measurement of BAL HBD2 may serve as a valuable marker for BOS.