Background: Proton (H+) secretion and the HVCN1 H+ channel are part of the innate host defense mechanism of the airways. The objective of this study was to determine H+ secretion in asthmatic and nonasthmatic patients with chronic rhinosinusitis (CRS) in freshly excised human sinonasal tissue. Methods: Nasal or sinus mucosa from subjects with three different conditions (normal, CRS, and CRS with asthma) was harvested during sinus surgery. The equilibrium pH and the rate of H+ secretion were measured in an Ussing chamber using the pH-stat titration technique. Results: Nasal epithelia isolated from subjects with CRS and asthma had a mucosal equilibrium pH = 6.95 (n = 5), which was significantly lower than in normal subjects (7.35 ± 0.21; n = 5) or from subjects with CRS without asthma (7.33 ± 0.15 In = 5). Nasal epithelia from CRS with asthma (n = 5) secreted H+ at a rate of 135 ± 46 nmol•min -1•cm-2. This rate was significantly higher compared with normal (73 ± 39 nmol•min-1•cm-2; n = 8) or CRS without asthma (51 • 28 nmol• min-1• cm-2; n = 7). Mucosal addition of the HVCN1 blocker ZnCl2 blocked H+ secretion by 70% in normal, 53% in CRS without asthma, and by 51% in CRS with asthma. In contrast, measures in sinus tissues were unaffected by the disease condition. Conclusion: Freshly excised human nasal and sinus epithelia secrete acid. Nasal (but not sinus) tissues from asthmatic CRS patients showed lower mucosal pH values and higher rates of H+ secretion than CRS and normal subjects. The increased acid secretion might contribute to epithelial injury in CRS patients with asthma. Copyright © 2009, OceanSide Publications, Inc.