Due to the increased presence of macrophages in the lungs following HP influenza virus infection, replication of paired H1N1 and H5N1 viruses (Table 1 ) was assayed over time in primary human PBMC-derived macrophages and mouse lung macrophages to address whether these cells are specific targets of viral infection and can productively replicate HP viruses. Mouse lung macrophages were harvested from naive BALB/c mice and infected in vitro (MOI = 0.1, Figure 4A ) as described. While the HP 1918 and Thai/16 viruses exhibited a slight increase in log titer very early after inoculation (13-24 hrs p.i.), overall these viruses did not replicate efficiently compared to the growth kinetics of these viruses observed in lung epithelial cells [22, 24] . At titers and these differences were statistically significant (^p,0.05) at 72 hrs p.i.. The lack of prolific replication of these four viruses in primary mouse lung macrophages was confirmed further when a higher MOI (1.0) was utilized (data not shown). Human macrophages also supported replication of all four viruses ( Figure 4B , MOI = 0.1). At 48 hrs p.i. 1918 and Thai/16 infected macrophages exhibited 180 times higher virus titers than TX/91 and SP/83 infected cultures. Interestingly, 1918 virus-infected macrophages exhibited a higher baseline titer soon following infection that was found to be statistically significant when compared to the other infection groups ( { p,0.05). In summary, while human macrophages are a target of viral replication and support replication well, mouse lung macrophages support low levels of 1918 and Thai/16 virus production early following infection.