The aim of the present study was to examine the factors that contribute to the postmortem lung weight in acute fire fatalities (n=149) including those with lower (<60%) and higher (>60%) blood carboxyhemoglobin (COHb) levels (n=94 and 55, respectively). The control groups consisted of acute myocardial infarction/ischemia (AMI, n=99) and mechanical asphyxiation (n=85). For all cases (n=333), the lung and heart weights were independent of the postmortem time (4.5-72 h) and charring of the body. The combined weight of both lobes of the lung showed a significant gender difference (males>females, P<0.001), negative regression with respect to age (R=0.167, P<0.01) and positive regression with respect to heart weight (R=0.316, P<0.001). The gender difference was also significant for each cause of death even after being corrected using body height measurements. When the lung-heart weight ratio was estimated to diminish the influence of possible cardiogenic factors, the gender difference was insignificant for each cause of death among the non-elderly (<60 years of age). However, for elderly fire fatalities (>60 years of age), there was a gender difference (males>females) for the lower COHb group (P<0.05) and higher COHb group (P<0.001). A significant age-dependent difference (non-elderly>elderly) in the lung-heart weight ratio was observed for fire fatalities with a lower COHb and AMI among males and for fire fatalities with a higher COHb among females. Such gender- and/or age-dependent influences were not significant for fatal mechanical asphyxiation. These findings suggest that a person's heart weight may be a possible contributory factor to an increase in the lung weight in acute death, and that gender- and/or age-dependent susceptibilities may be additional factors that contribute to fire fatalities and AMI. In addition, elderly females appear to be most susceptible among fire casualties, and extreme cardiomegaly may also be a potential fatal risk factor.