Endothelial cell activation is an important step in the inflammatory cascade which leads to the extravasation of leukocytes into the site of inflammation. The rolling of leukocytes is the beginning of this cascade and is mediated by the selectins. We have analysed the binding of both polymorphonuclear granulocytes and mononuclear cells to E-selectin presented exclusively by activated vascular endothelial cells. Four different monoclonal antibodies inhibited this adhesion differentially, and deletion constructs of E-selectin expressed on endothelial cells were also functionally distinguishable by their interaction with granulocytes and lymphocytes, respectively. Different binding mechanisms for these leukocyte subsets to endothelial E-selectin are proposed and signalling mechanisms via E-selectin, in particular Ca²⁺ signals into the leukocyte will be discussed.