It has not been determined whether L-selectin-mediated rolling can promote leukocyte adhesion in vivo independent of P- and E-selectin. We used intravital microscopy of E- and P-selectin double-mutant mice (E−/P−) stimulated with tumor necrosis factor-α for 6–8 h to investigate the importance of L-selectin-dependent rolling in cremaster muscle venules. Rolling leukocyte flux in E−/P− mice was 9 ± 2 cells/min compared with 77 ± 17 cells/min in wild-type (WT) mice. Pretreatment with the L-selectin monoclonal antibody MEL-14 significantly reduced rolling in both E−/P− (by 89%) and WT mice (by 79%). L-selectin-dependent rolling in E−/P− mice resulted in leukocyte adhesion comparable to that seen in WT mice. MEL-14 pretreatment of E−/P− mice reduced leukocyte adhesion by 50%. The majority (∼80%) of intravascular leukocytes in both WT and E−/P− mice were neutrophils. We conclude that L-selectin can mediate rolling that results in sufficient leukocyte recruitment to account for the robust inflammatory response seen in E−/P− mice at later times.