BACKGROUND There is accumulating evidence that air pollution causes lung cancer. Still, questions remain about exposure misclassification, the components of air pollution responsible, and the histological subtypes of lung cancer that might be produced. METHODS We investigated lung cancer incidence in relation to long-term exposure to three ambient air pollutants and proximity to major roads, using a Canadian population-based case-control study. We compared 2,390 incident, histologically confirmed lung cancer cases with 3,507 population controls in eight Canadian provinces from 1994 to 1997. We developed spatiotemporal models for the whole country to estimate annual residential exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) over a 20-year exposure period. We carried out a subanalysis in urban centers, using exposures derived from fixed-site air pollution monitors, and also examined traffic proximity measures. Hierarchical logistic regression models incorporated a comprehensive set of individual and geographic covariates. RESULTS The increase in lung cancer incidence (expressed as fully adjusted odds ratios [ORs]) was 1.29 (95% confidence interval = 0.95-1.76) with a ten-unit increase in PM2.5 (μg/m), 1.11 (1.00-1.24) with a ten-unit increase in NO2 (ppb), and 1.09 (0.85-1.39) with a ten-unit increase in O3 (ppb). The urban monitor-based subanalyses generally supported the national results, with larger associations for NO2 (OR = 1.34; 1.07-1.69) per 10 ppb increase. No dose-response trends were observed, and no clear relationships were found for specific histological cancer subtypes. There was the suggestion of increased risk among those living within 100 m of highways, but not among those living near major roads. CONCLUSIONS Lung cancer incidence in this Canadian study was increased most strongly with NO2 and PM2.5 exposure. Further investigation is needed into possible effects of O3 on development of lung cancer.