nasal carriage is transient in most humans and usually benign, but dissemination of to extranasal sites causes the majority of clinical infections, and is a major cause of serious infections in the United States. A better understanding of innate nasal decolonization mechanisms is urgently needed, as are relevant models for studying clearance. Here, we screened a population of healthy smokers for nasal carriage and compared the participants' abilities to clear experimentally applied nasal before and after completion of a smoking cessation program. We determined that cigarette smoking increases the mean nasal load (2.6 Ă 10 CFU/swab) compared to the load observed in healthy nonsmokers (1.7 Ă 10 CFU/swab) and might increase the rate of nasal carriage in otherwise-healthy adults: 22 of 99 smokers carried at the screening visit, while only 4 of 30 nonsmokers screened positive during the same time period. Only 6 of 19 experimental inoculation studies in active smokers resulted in clearance within the month of follow-up, while in the cessation group, 6 of 9 subjects cleared nasal and carriage duration averaged 21 ± 4 days. Smoking cessation associated with enhanced expression of -associated interleukin-1ÎČ (IL-1ÎČ) and granulocyte colony-stimulating factor (G-CSF) in nasal fluids. Participants who failed to clear exhibited a higher nasal load and elevated nasal interleukin-1 receptor antagonist (IL-1RA) expression at the preexperiment study visits. We conclude that smokers exhibit higher loads than nonsmokers and that innate immune pathways, including G-CSF expression and signaling through the IL-1 axis, are important mediators of nasal clearance.