The effects of rat CINC/gro, a member of the interleukin-8 family, on the endothelium-neutrophil interaction and transendothelial macromolecular leakage were studied in rat mesenteric microcirculation. Thirty minutes after superfusion with 10 nM CINC/gro, the number of neutrophils adherent to the venular endothelium and those migrated across the venules were significantly increased with a concomitant elevation of luminol-dependent chemiluminescence at the site of adhesion. Transendothelial macromolecular leakage as assessed by the relative length of venular wall stained with monastral blue B was also increased at 30 min after the start of CINC/gro superfusion. Pretreatments with a CD18-directed monoclonal antibody, WT-3 (1 mg/kg), significantly attenuated the increase in number of adherent and migrated neutrophils, the increase in luminol-dependent chemiluminescence, and the venular macromolecular leakage after the application of CINC/gro. These data suggest that CINC/gro is a novel stimulator that evokes not only locomotive but also secretagogue activation of neutrophils via a CD18-dependent mechanism in vivo.