Chemoprevention by dietary and pharmacological means provides a strategy for attenuating the health risks resulting from cigarette smoking and in particular from passive exposure to environmental cigarette smoke (ECS). We evaluated the ability of the glucocorticoid budesonide and of the natural agent phenethyl isothiocyanate (PEITC) to affect DNA damage in bronchoalveolar lavage (BAL) cells of CD-1 mice exposed to ECS, starting within 12 h after birth and continuing until the end of the experiment. After weanling, based on a preliminary subchronic toxicity study, groups of mice received daily either budesonide (24 mg/kg diet) or PEITC (1,000 mg/kg diet). After 2 weeks of treatment, all mice were sacrificed and subjected to BAL, mainly recovering pulmonary alveolar macrophages. Evaluation of single-cell DNA strand breaks was made by using the alkaline-halo test, a modification of the comet assay. The analysis of 481 BAL cells yielded the following results (expressed as nuclear spread factor): (a) Sham-exposed mice: mean 0.84 (lower-upper 95% confidence intervals 0.74-0.94); (b) ECS-exposed mice: 2.77 (2.46-3.09); (c) ECS-exposed mice treated with PEITC: 1.15 (1.05-1.26); (d) ECS-exposed mice treated with budesonide: 1.37 (1.25-1.49). Thus, exposure to ECS resulted in a significant increase of DNA damage as compared with sham, and both PEITC and budesonide significantly attenuated this damage. In conclusion, the analysis of sentinel cells collected by BAL, a semi-invasive technique that is commonly used in humans for diagnostic purposes, showed that the investigated chemopreventive agents are able to revert the DNA damage produced by passive exposure to cigarette smoke.