Consistently high titers of human influenza viruses in ocular samples following both i.n. and i.o. inoculation indicates that these H1N1 and H3N2 viruses are not exhibiting a preferential tropism for ocular infection but more likely are a reflection of the high titers observed in the upper respiratory tract in these tissues independent of the initial inoculation route. Specifically, the nasolacrimal duct which links the ocular lacrimal sac to the nasal meatus could serve as a conduit for virus-containing fluid exchange between ocular and respiratory tract tissue [18] . Numerous reports have documented drainage of vaccine or immunizing agents to nasal tissue following topical ocular administration as well as the spread of intranasally administered solutions to the conjunctival mucosal surface [18, 45] . However, spread of virus from respiratory tract tissue to ocular tissue following i.n. inoculation with human or avian influenza viruses has not been observed previously in the ferret and only sporadically reported in the mouse, possibly due to relatively low titers of virus in nasal tissue or other anatomical differences [20, 24, 26, 46] . Detection of both human and avian influenza viruses in ferret eyes and conjunctival tissue following i.n. inoculation indicates that virus can circulate proximal to the nasal cavity and nasolacrimal canal more readily than previously considered and that more routine collection of ocular tissue during standard virus pathotyping in mammalian models is warranted to better understand the extent of viral ocular dissemination (Table 4 ). While it is unlikely that ferret grooming practices are solely responsible for virus spread between these locations, human studies with numerous respiratory viruses have demonstrated the ability to self-inoculate between ocular and respiratory sites, and it is possible that self-inoculation could be further contributing to virus spread in this model [47, 48] . Inoculation of ferrets by the ocular route with 10 6 EID 50 of selected human and avian influenza viruses in a 20 ml volume resulted in comparable results to those obtained employing a 100 ml inoculation volume, indicating that replication-independent drainage of virus to respiratory tract tissue and subsequent virus detection in NW and CW samples reported in this study was not contingent on the inoculum volume (data not shown).