To assess the association between air pollution and health-related quality of life (HRQOL), we performed an ecological study by a two-stage stratified random sampling of the Japanese general population. A total of 3395 subjects, aged 16 and older, filled out questionnaires, including the Medical Outcomes Study Short Form-36 Health Survey (SF-36). Air pollutants examined in this study were nitrogen oxides (NOx) and suspended particulate matter (SPM). We used analysis of covariance to estimate the mean differences for each SF-36 domain among four groups categorized according to concentrations of air pollutants to which they were exposed. We observed a significant linear trend of a lower 'vitality' domain score in the SF-36 in groups exposed to higher concentrations of NOx (p = 0.013). The results of the present study are important for, and needed by, public health policy makers, because assessing the health effects of air pollution by measuring the HRQOL would provide a new method for formulating air pollution policies.