In this study we quantified influenza associated mortality risks at the various ranges of temperature and humidity, and compared the results between two large subtropical cities. An increasing pattern of influenza-associated mortality risks on all-cause and cardiorespiratory along the low to high periods was found for temperature, relative and absolute humidity in both cities during the period of 2004-2006. The interaction between vapor pressure indicators and virus activity were also consistently significant for relative and absolute humidity. Although lower vapor pressure (or temperature) has been found to facilitate virus transmission and survival in the guinea pig model [10] , our results suggested that higher vapor pressure (or temperature) was associated with a higher mortality risk attributable to influenza. Severity of seasonal influenza epidemics were not only determined by virus transmission efficiency and outdoor weather conditions, but also largely affected by host resistance, indoor living environment and social behavior [5] . The high vapor pressure periods coincided with the summer peaks of influenza in both Guangzhou and Hong Kong, indicating that influenza could pose a higher risk when reaching its peak in seasons with high vapor pressure in subtropical cities. Our results may help to interpret our previous findings that the effects of influenza were significantly higher in the humid and warm spring/summer period than in the dry and cold winter period in Hong Kong [16] . The extreme low vapor pressure was usually recorded during December-January and the highest appeared during June-July, which coincided with the trough and peak periods of excess risks associated with influenza viruses. Effect modification of environmental factors was only detected in all-cause and cardiorespiratory mortality, but not in pneumonia and influenza, suggesting that the synergistic interaction between high humidity (or temperature) and virus activity may mainly lie in their similar regulation pathways in cardiovascular systems. These results are also in agreement with our previous findings that pneumonia and influenza mortality risks attributable to influenza did not exhibit a seasonal variation [16] . Extreme heat has been documented to increase blood viscosity through evaporation of body fluid and trigger intravascular coagulation through damaging endothelial cells [24] . Influenza infection has a similar pro-thrombotic effect by inducing inflammation around blood vessels and rupturing atherosclerotic plaques [25] . As a result, mortality risks would be dramatically raised by the stress of both extreme weather and influenza infections. The results suggested that we need extra precautionary measures to reduce influenza infections in people with cardiovascular diseases, especially under the frequent hot and humid weather conditions experienced in the tropical and subtropical areas. Although the experiments of influenza virus transmission between guinea pig hosts found the higher transmission rates occurred under dry air (vapor pressure below 10hPA) [10] , our results indicated that the mortality risks associated with influenza under the low vapor pressure environment were lower than the rest of study period. The reason could be the short time of exposure to the very low level of vapor pressure. During our study period there were only 2 and 13 weeks with an average vapor pressure below 10hPA in Hong Kong and Guangzhou, respectively. Most weekly average vapor Percentage change (%) of mortality counts for all-cause and cardiorespiratory (CRD) mortality. The risks associated with 1% increase in influenza virus activity during the low-, middle-and high-vapor pressure periods were plotted for the age groups younger than 65 years (< 65) and equal or over 65 years (≥65). The 95% confidence intervals were shown in vertical bars. An asterisk is added above the bars if the interaction between vapor pressure and influenza is shown statistically significant by the likelihood ratio test between main effects and interaction models. pressures during the low vapor pressure period were within the range of 10-20hPA, in which the guinea pig experiments showed dramatically reduced transmission rates [10] . In future, we may examine the seasonal variation in influenza effects in other cities to assess whether such a seasonal variation, if common in subtropical and tropical cities, is consistently determined by environmental factors, or by other factors such as host immunity and virus virulence. The results for the different age groups suggested that the modification effects of environmental factors may mainly lie in the elderly aged over 65 years, as the consistent increasing trend over the low to high vapor pressure periods was only observed in this age group. However, since over 65% of deaths occurred in this age group for both cities (Table 1 ), the small numbers of weekly death counts in the younger age group (< 65 years) may not have had enough power to allow assessment of effect modification based on the data over the 3 years. A future study with a long study period or a large population may help answer whether young people maybe also expose to higher mortality risks during the hot and humid days.