Given our previous studies showing that the Toll-like receptor 4 (TLR4) antagonist Eritoran (E5564), as well as other structurally unrelated TLR4 antagonists, blocked influenza-induced acute lung injury (ALI) in wild-type (WT) mice and in cotton rats (12, –, 15), we sought to determine if such treatment would also mitigate the increased susceptibility of the host to secondary (2°) bacterial infection. This evidence concerns the gene TLR4 and bacterial infectious disease.