Lung consolidation has been described as a pathological feature of severe influenza virus infection caused by the 1918 pandemic virus and H5N1 viruses in humans [9, 25, 26] as well as in animal models [11, 12, 18] . Using a detailed flow cytometry evaluation, the current study set out to characterize differences in the cellular innate immune response in the mouse lung following highly pathogenic (HP) or low pathogenicity (LP) influenza virus infections. Lungs from mice infected with the HP 1918 H1N1 virus and a recent H5N1 human isolate (A/Thailand/16/04 (Thai/16)) exhibited a significant increase in cellularity in comparison to the LP seasonal H1N1 isolate, A/Texas/36/91 (TX/91). Significant differences in titer between HP and LP virusinfected mice were observed as early as day 1 post-inoculation (p.i.), likely forecasting the dramatic increase in immune cell infiltration in the lungs of these virus-infected mice. Interestingly at day 7 p.i. when peak lung cellularity was observed in HP virus infection groups, differences in virus titers between paired subtype viruses (1918 compared to TX/91 and Thai/16 compared to SP/ 83) were minimal and were limited to a maximum difference of 1 log (Figure 1 ), indicating a failure by the immune system to clear the viral infection. Lung cellularity was further investigated by characterizing the comprising immune cell sub-populations. We observed a significant increase in macrophages and neutrophils early following infection with the 1918 and Thai/16 viruses, and their sustained presence in the lung tissue mark a distinction between HP and LP influenza virus infection. These data show that virus replication in the lungs of HP influenza infections are sustained at high levels the first week of infection regardless of the high numbers of immune cells present in the tissue. Although the current study did not determine whether these cells are playing an antiviral role against the HP viruses, it has been previously shown that neutrophils and macrophages assist in the clearance of influenza virus early during infection; these cells appear to be capable of only partially reducing the virus load in the lung despite their presence at high numbers [20] . We also observed a decrease in the percentage of lung-associated dendritic cells and T cell lymphocytes during HP influenza virus infection. A decrease in the number of circulating lymphocyte populations has also been previously observed in the peripheral blood of humans and mice infected with H5N1 viruses [5, 9, 10, 15, 20, 27] . The precise mechanism of leukocyte depletion during H5N1 infections is not well understood, but evidence of apoptosis in the spleen and lungs of HP H5N1-infected mice detected in situ suggests a mechanism for cell loss [16] .