ABSTRACTObjective:The selectins are a family of adhesion molecules that mediate leukocyte rolling, a prerequisite for their later firm adhesion and migration to sites of inflammation. The N‐terminal lectin domain of selectins is important for Ca2+‐dependent binding to oligosaccharide ligands. We set out to study the effect of peptides corresponding to residues 11–20, 23–30, 36–50, 54–63, 70–79 and 109–118 (counting from the N‐terminus of the mature proteins) of the lectin domain of human L‐, P‐ and E‐selectins on leukocyte rollingin vivo.Methods:Peptides were applied by local intravascular microinfusion via a glass micropipette into rat mesenteric venules. Visibly rolling cells were counted off‐line and compared with rolling cells counted during control periods.Results:Peptides corresponding to residues 70–79 of P‐selectin and 11–20 of L‐selectin reduced leukocyte rolling flux in rat mesenteric venules to less than 30% of that measured during control infusion. Peptides corresponding to residues 109–118 of P‐selectin, 54–63 of L‐selectin and 23–30 of E‐selectin also reduced leukocyte rolling flux, although to a lesser degree.Conclusions:We have shown that small peptides based on the lectin domain of all three selectins can be eff