Although regional differences in lung cancer mortality are likely to be attributable to regional differences in tobacco smoking, studies in various countries found only weak relationships. This paper aimed at explaining regional differences in lung cancer mortality in the Netherlands. In a first step, clues for the role of smoking were obtained from a detailed description of regional mortality differences. These differences were found to be strongly determined by cohort effects: they vary between birth cohorts, and have been stable for over 30 years. Regional mortality differences reflect a diffusion of the lung cancer epidemic from high-income regions to low-income regions. These findings are suggestive of a relationship with regional differences in trends in cigarette smoking. In a second step, by means of multiple regression analysis, mortality differences in 1980–84 were related to available data on cigarette smoking and two other possible risk factors: work in transport and manufacturing industry, and air contamination. The independent variables referred to the 1970s. Positive associations with various smoking measures were found for women, but for men the associations were weak or non-existent. Mortality differences among men 45–64 years were associated with work in transport and manufacturing industry. Strong associations wi