Conclusions This study reports novel data on the response of IAV in droplets of model media to varying RH, including extreme conditions that have never been studied, and for the first time presents the relationship between IAV viability in human mucus and humidity over a large range of RH. Results suggest that there exist three regimes of IAV viability defined by RH. We provide a mechanistic explanation for these regimes, based on droplet evaporation, a subsequent increase in solute concentrations in the droplet, and their effect on the virus. Our theory also explains the conflicting findings in the literature about IAV viability in airborne droplets [8], [13]–[15]. We further outline a new perspective on the dependence of IAV’s transmission on humidity, which introduces a possible explanation for influenza’s seasonal patterns in different regions.