Even in primed animal models, lethal doses of LPS are high, approximately 100 μg/kg, generating estimated plasma concentrations of ∼1 μg/ml. These plasma levels are still >100-fold that found in even the most extreme cases of human sepsis (65) . Because the dose of E5564 required to protect against LPS is proportional to the LPS challenge dose, studying E5564 in these animal models indicates that E5564 can be a safe and effective antagonist even under these extraordinary conditions. E5564 is approximately tenfold better in human blood than mouse blood (IC 50 =1.6 nM in human whole blood; Table I versus ∼20 nM in mouse whole blood; Table II) .