To examine the capacity of influenza viruses to cause severe disease following ocular inoculation, and to better identify those features specific to ocular inoculation, we inoculated ferrets by either the traditional i.n. route (using a 1 mL inoculation volume) or the i.o. route (using a 100 ml inoculation volume) with 10 6 EID 50 of NL/219, NL/230, or Brisbane virus and collected systemic tissues on day 3 p.i. (Table 3 and 4). While i.n. inoculation with the H7N7 viruses tested in this study results in high virus titers throughout the respiratory tract of ferrets, H7N7 virus dissemination following i.o. inoculation was generally restricted to the upper respiratory tract, with a .3 log reduction in titers in nasal turbinates (p,0.05) and only sporadic virus isolation in trachea and lung samples compared with intranasal inoculation (p,0.005) ( Table 3) . A similar pattern of virus dissemination following H7N7 i.o. virus infection was observed when ferrets were inoculated by the i.n. route using a 100 ml and not 1 mL inoculation volume ( Table 3 ). The H1N1 virus Brisbane replicated with comparable efficiency in nasal turbinate samples regardless of the inoculation route or volume chosen, but similar to H7N7 virus ocular infections, did not consistently replicate to high titers in lower respiratory tract tissues. Unlike virus dissemination to the respiratory tract, virus spread to the intestinal tract was not contingent on the route or volume of inoculation.