The severity of epidemic and pandemic influenza outbreaks is dictated in part by the efficiency with which the causative strain transmits between human hosts. The mechanisms underlying influenza virus spread are poorly understood, in part because of the lack of a convenient animal model to study this phenomenon. Indeed, despite extremely efficient transmission among humans and virulence in the mouse model, we have shown that even the 1918 pandemic influenza virus does not transmit between mice. We therefore evaluated the guinea pig as a model mammalian host for influenza virus. Using the recent human isolate A/Panama/2007/99 (Pan/99) (H3N2) virus, we found that guinea pigs were highly susceptible to infection with the unadapted virus (ID(50) = 5 plaque-forming units). Pan/99 virus grew to high titers in the upper respiratory tract and was shed in nasal washings of infected animals. Moreover, influenza virus was transmitted from infected guinea pigs to noninfected guinea pigs housed in the same cage, an adjacent cage, and a cage placed 91 cm away. Our results demonstrate that influenza virus can pass between guinea pigs by means of droplet spread and thereby establish the suitability of the guinea pig as a model host for influenza virus transmission studies.