Despite restriction of virus following i.o. inoculation to upper respiratory tract tissues compared with traditional 1 mL intranasal inoculation through day 3 p.i., virus introduced by the ocular route was still capable of causing lethal disease, as ferrets inoculated with the HPAI H5N1 virus Thai/16 by the ocular route required euthanasia days 7-8 p.i. due to development of neurological signs (Table 1) . Ferrets which succumbed to Thai/16 virus infection following ocular inoculation exhibited pronounced lymphopenia in peripheral blood and systemic spread of virus to all regions of the respiratory tract and brain comparable to 1 mL intranasal inoculation, albeit with reduced lethargy and a delayed time-to-death ( [32] and data not shown). These data suggest that ferrets inoculated by the ocular route succumb to a similar course of disease as intranasally inoculated ferrets, however following i.o. inoculation there is a delay in both the kinetics of virus dissemination and the development of neurological signs and severe disease, potentially owing to differences in virus inoculum reaching lower respiratory tract tissues at the time of ocular inoculation.