CC10, the secretory product of bronchiolar Clara cells, is infrequently expressed in non -small cell lung cancer (NSCLC), and its overexpression in NSCLC cell lines results in a less malignant phenotype. CC10 levels in bronchoalveolar lavage fluid (BAL) and serum are significantly lower in current smokers than healthy nonsmokers, but the effect of long-term smoking cessation on CC10 is unknown. We measured CC10 in baseline BAL and plasma collected from current (n = 81) and former (n = 23) smokers participating in a chemoprevention trial. Former smokers had significantly higher plasma CC10 levels compared with current smokers [mean, 62.1 ng/mL (95% CI, 43.0-81.2); range, 23.0-175.0 ng/mL for former smokers; and mean, 37.1 ng/mL (95% CI, 29.8-44.4); range, 5.0-171.0 ng/mL for current smokers; P < 0.001]. BAL CC10 levels also trended in the same direction. A significant positive correlation was found between CC10 plasma and BAL levels. After adjustment for age, sex, and pack-years of cigarette consumption, former smokers had 1.70 (95% CI, 1.23-2.36) times higher plasma CC10 levels than current smokers (P < 0.01), whereas former smokers also had nonsignificantly higher baseline BAL CC10 levels compared with current smokers [adjusted mean ratio (95% CI), 1.60 (0.92-2.80), P = 0.094 and 1.35 (0.86-2.10), P = 0.193 for the absolute and normalized BAL CC10, respectively]. These results show that sustained smoking cessation is associated with higher plasma CC10 levels, suggesting that at least some of the damage associated with tobacco smoke may be repaired by long-term smoking cessation. (Cancer Epidemiol Biomarkers Prev 2007;16(3):577 -83)