To evaluate the role of cell adhesion molecule ICAM-1 in West Nile virus (WNV) infections, an in-vivo murine model was utilized. Wild-type and ICAM-1 deficient mice were infected with the WNV NY99 strain via subcutaneous inoculation in the footpad and assessed for survival and viral titer in the brain. All mice deficient in ICAM-1 reached ethical endpoints by day 10 post infection whereas 40% of wild-type mice survived until the conclusion of the study. Brain homogenates indicated that viral titers were two logs greater in ICAM-1 deficient mice compared to the wild-type. Together, this data suggests that ICAM-1 is critical for mouse survival and limits viral titer in the brain.