Most infections with influenza virus result in respiratory disease. However, influenza viruses of the H7 subtype frequently cause ocular and not respiratory symptoms during human infection, demonstrating that the eye represents an alternate location for influenza viruses to infect humans. Using a ferret model, we studied the ability of influenza viruses to cause disease following ocular inoculation. We found that both human and avian influenza viruses could use the eye as a portal of entry to establish a respiratory infection in ferrets. Influenza viruses were also detected in ocular samples taken from ferrets during virus infection. We identified that influenza viruses spread to different tissues in ferrets when inoculated by ocular or respiratory routes, and that these differences affected the transmissibility of influenza viruses in this model. This study is the first to confirm that virus can spread from the eye to the respiratory tract in a replication-independent manner, and offers greater insight in understanding the ability of influenza viruses of all subtypes to cause human infection by the ocular route. Figure 3 ). Ocular inoculation with all H7 influenza viruses tested resulted in elevated peak mean viral titers in NW samples and a higher incidence of detection in CW samples compared with H5N1 viruses (45% positive among H7 virus samples compared with 25% of H5 virus samples) (Table 2, Figure 2 ). However, despite reduced viral replication in NW samples, H5N1 viruses were capable of causing .20% weight loss and lethal disease in ferrets following i.o. inoculation (Table 1) . Interestingly, all seasonal H1N1 and H3N2 viruses evaluated were detected at high titer in both NW and CW samples; i.o. inoculation with Mex/4108, Brisbane, and Panama viruses, along with the H7N7 NL/230 virus, resulted in the highest peak mean titers in CW samples (.10 3 EID 50 /ml) compared with all viruses examined (Table 2, Figure 2 ). All viruses with the exception of Thai/16 virus were also detected at low titer in RS samples, with peak titers 10 1.8 -10 2.7 EID 50 /ml observed days 3-7 p.i. (Table 2 ).