Background: The increasing evidence for rapid global climate change has highlighted the need for investigations examining the relationship between weather variability and infectious diseases. However, the impact of weather fluctuations on hand, foot, and mouth disease (HFMD), which primarily affects children, is not well understood. Methods: We acquired data related to cases of HFMD and weather parameters of temperature and humidity in Fukuoka, Japan between 2000 and 2010, and used time-series analyses to assess the possible relationship of weather variability with pediatric HFMD cases, adjusting for seasonal and interannual variations. Results: Our analysis revealed that the weekly number of HFMD cases increased by 11.2% (95% CI: 3.2-19.8) for every 1 degrees C increase in average temperature and by 4.7% (95% CI: 2.4-7.2) for every 1% increase in relative humidity. Notably, the effects of temperature and humidity on HFMD infection were most significant in children under the age of 10 years. Conclusions: Our study provides quantitative evidence that the number of HFMD cases increased significantly with increasing average temperature and relative humidity, and suggests that preventive measures for limiting the spread of HFMD, particularly in younger children, should be considered during extended periods of high temperature and humidity. (C) 2011 Elsevier B.V. All rights reserved.