Lung cancer is a common malignancy in Hong Kong. The incidence in males is ranked medium, but that in females is among the highest in the world. More than 60% of female patients are lifelong nonsmokers, implying that carcinogenic mechanisms other than cigarette smoking may be involved in the development of lung cancers in female nonsmokers. To identify the candidate tumor suppressor genes involved, we screened 50 commonly deleted regions of all the chromosomal arms for loss of heterozygosity of microsatellite markers in 41 samples of cancerous lung tissue from nonsmokers. We found frequent allelic loss of 50–62.5% in the chromosomal regions 1q21–31, 3p14.2, 7q31, 8p21, 10q26, 13q12.3, 16q24, 17p13.1–13.3, 17q13.3, 18q23 and 19p13. Comparison with 40 lung cancers from smokers using the same markers showed a similar range of loss of heterozygosity frequency in the two populations. We found that some regions commonly deleted in smokers (for example, 4q32, 6q27, 9q21 and 11q23) were statistically less frequently deleted in nonsmokers, but we found no region frequently deleted in nonsmokers but not smokers. Our data on cancers from smokers indicate that smoking induces widespread genomic damage, leading to extensive chromosomal loss of long segments of DNA. Cancers from nonsmokers exhibit more targeted damage, with fewer and shorter segments of DNA loss. The deleted regions in cancers of nonsmokers might represent the essential complement of genetic material that must be lost for lung cancers to develop.