A key endothelial receptor in leukocyte-endothelial cell (EC) interactions is ICAM-1. ICAM-1 is constitutively expressed at low levels on vascular endothelial cells and its levels significantly increase following stimulation with many pro-inflammatory agents. This study provides evidence that in inflamed arterioles of anesthetized mice (65 mg/kg Nembutal, ip), ICAM-1 mediates leukocyte rolling, in contrast to its expected role of mediating firm adhesion in venules. The number of leukocytes rolling on arteriolar EC is decreased in ICAM-1 knockout (KO) compared to wild type (WT) mice (KO: 6.0±0.9; WT:12.0 ±1.0 leukocyte/40sec, p<0.05), while the leukocyte rolling number in venules remains unaffected (KO: 5.6 ±0.9; WT: 7.0 ±0.7 leukocyte/40sec, n=13-15 sites). We also show that the fraction of leukocytes that is rolling on arteriolar EC does so with a higher characteristic velocity (>70µm/sec), and, further, that the distance over which rolling contacts with the arteriolar wall are maintained is ICAM-1 dependent. In ICAM-1 KO animals or in WT mice in the presence of ICAM-1 blocking antibody, leukocytes rolled significantly shorter distances over the sampled 200µm vessel length compared to WT (68±6.7 and 55± 9.4 vs 85±12.9 % total, respectively, n=4 sites, p<0.05). We also found evidence that in ICAM-1 knockout mice, a significant fraction of leukocyte rolling and adhesive interactions with arteriolar ECs could be accounted for by upregulation of another adhesion molecule, VCAM-1, providing an important illustration of how expression of related proteins can be altered following genetic ablatement of a target molecule (in this case ICAM-1).