The Initial rolling Interaction of leukocytes with the blood vessel wall during leukocyte trafficking has been postulated to rely on members of the selectin family of adhesion molecules. Two selectins, E-selectln and P-se&tin, have been Identified that are expressed on activated endothelial cells. Mice deficient In E-se&tin expresalon have been produced in order to examine the role of this selectln In leukocyte trafficking. Mice homozygoua for an E-selectln null mutation were viable and exhibited no obvious developmental alterations. E-seiectln-deflclent mice displayed no signlficant change In the trafficking of neutrophlls In several models of Inflammation. However, blocking both endothellal wlectina by treatment of the E+ lectlndeflclent animals with an anti-murlne P-selectln antlbody, 5H1, aignlficantly lnhlblted neutrophll emlgratlon In two dlstlnct models of lnflammatlon. While neuwophll accumulatkm at early times during thloglycollete-Induced peritonitis was dependent on P-selectin, neutrophll accumulation at later time points was blocked by 5Hl only In E-selectln-deflclent mice but not in wild-type mice. Similarly, edema as well as leukocyte accumulation In a model of delayed-type hypersensitlvlty in the skin was almost completely prevented by blockade of P-se&tin function wlth 5Hl in the E-selectln-deflclent mice while the same treatment had no effect In wild-type mice. These data demonstrate that the majority of neutrophll migration in both models requires an endothellal selectin but that E-se&tin and P-selectln are functionally redundant. These data have Important impllcatlons In the use of selectln antagonists In the treatment of inflammatory disease.