A clinical isolate of influenza A/Hong Kong/8/68 (H3N2) (A/ HK; Mouse Lung Pool 11-29-05) virus that had been passaged at least nine times through mice was stored as frozen stock (2.8610 7 TCID 50 /ml) in the supernatant of mouse lung homogenates [29] . Stock was diluted 1:300-1:1,000 in 0.05% gelatin in Eagle's minimal essential medium (Sigma-Aldrich) and aerosolized for 20 min to achieve LD 90 -LD 100 (target 100 TDIC 50 /mouse). Viral concentration in the nebulizer before and after aerosolization and in lung homogenates was determined by hemagglutination assay of infected MDCK cells [30] . In some experiments, 1 g of ribavirin was dissolved in 10 ml of NTHi lysate prior to aerosolization. Final ribavirin and lysate protein concentrations were 100 mg/ml and 2.5 mg/ml, respectively. Mice were challenged without pretreatment, following pretreatment on day 21, or following pretreatment on days 27, 24 and 21. On day 0, all groups of mice were exposed to the same viral aerosol. On day +4, 5 mice from each group were sacrificed and their lungs removed. Lungs were homogenized by beadbeating and the levels of virus determined. Remaining mice in each group were observed daily for up to 21 days for overt illness, morbidity and mortality. Mice were weighed on days 0 and +4, and three times weekly from day +7 until day +21.