We have performed comparative studies of the infection kinetics of human and avian influenza viruses in a model of human ciliated airway epithelium at temperatures reflective of the human proximal and distal airways. Our data show that avian and avianized influenza viruses are restricted for infection and growth in HAE at 32uC but not 37uC, while human viruses infect and grow efficiently at both temperatures. Based on these data, we suggest that while the warmer temperatures of the distal airways enable comparable infection by both human and avian influenza viruses, the cooler temperatures of the human proximal airways only support efficient and robust infection of the ciliated airway epithelium by human influenza viruses. We speculate that the observed restriction for avian and 'avianized' viruses in HAE would render avian influenza viruses more susceptible to innate and adaptive immune responses that limit pathogenicity in vivo.