Sick building syndrome (SBS) is an increasingly common health problem for workers in modern office buildings. It is characterized by irritation of mucous membranes and the skin and general malaise. The impact of environmental tobacco smoke (ETS) exposure and overtime work on these symptoms remains unclear. The authors examined these relations using data from a 1998 cross-sectional survey of 1,281 municipal employees who worked in a variety of buildings in a Japanese city. Logistic regression was used to estimate the odds ratio for symptoms typical of SBS while adjusting for potential confounders. Among nonsmokers, the odds ratio for the association between study-defined SBS and 4 hours of ETS exposure per day was 2.7 (95% confidence interval: 1.6, 4.8), and for most symptom categories, odds ratios increased with increasing hours of ETS exposure. Working overtime for 30 or more hours per month was also associated with SBS symptoms, but the crude odds ratio of 3.0 for SBS (95% confidence interval: 1.8, 5.0) was reduced by 21% after adjustment for variables associated with overtime work and by 49% after further adjustment for perceived work overload. These results suggest that both ETS exposure and extensive amounts of overtime work contribute to the development of SBS symptoms and that the association between overtime and SBS can be explained substantially by the work environment and personal lifestyle correlated with overtime.