We assessed associations between indicators for moisture in office buildings and weekly, building-related lower respiratory and mucous membrane symptoms in office workers, using the U.S. EPA BASE data, collected in a representative sample of 100 U.S. office buildings. We estimated the strength of associations between the symptom outcomes and moisture indicators in multivariate logistic regression models as odds ratios (ORs) and 95% confidence intervals (CI), controlling for potential confounding factors and adjusting for correlation among workers in buildings. This analysis identified associations between building-related symptoms and several indicators of moisture or contamination in office buildings. One set of models showed almost a tripling of weekly building-related lower respiratory symptoms in association with lack of cleaning of the drip pans under air-conditioning cooling coils (OR [CI] = 2.8 (1.2-6.5)). Other models found that lack of cleaning of either drip pans or cooling coils was associated with increased mucous membrane symptoms (OR [CI] = 1.4 (1.1-1.9)). Slightly increased symptoms were also associated with other moisture indicators, especially mucous membrane symptoms and past water damage to building mechanical rooms (OR [CI] = 1.3 (1.0-1.7)). Overall, these findings suggest that the presence of moisture or contamination in ventilation systems or occupied spaces in office buildings may have adverse respiratory or irritant effects on workers. The analysis, however, failed to confirm several risks identified in a previous study, such as condition of drain pans or outdoor air intakes, and other hypothesized moisture risks. Studies with more rigorous measurement of environmental risks and health outcomes will be necessary to define moisture-related risks in buildings.