The aim of the study was to assess the mechanisms through which leukocyte deactivation occurs upon hemorrhagic shock. In particular, the influence of β-adrenergic tone was evaluated. BALB/c mice were hemorrhaged and resuscitated 60 min after hemorrhage. Animals were sacrified 60 min later by exsanguination. Blood from exsanguination was cultured ex vivo with lipopolysaccharide (LPS) and heat-killed Staphylococcus aureus Cowan I (SAC). Hemorrhage resulted in a major decrease of LPS-induced TNF production whereas IL-10 production was significantly enhanced. Selective β2-adrenoceptor antagonists (ICI 118,551) attenuated the decrease in TNF production and further enhanced IL-10 production. Hemorrhage did not alter SAC-induced TNF production levels whereas IL-10 production was increased. ICI 118,551 further increased the production of both TNF and IL-10. These data suggest that leukocyte deactivation after LPS stimulation is not a generalized phenomenon since TNF production was maintained when another microbial activator was used. IL-10 production was enhanced after hemorrhagic shock, independently of the nature of the trigerring agent. Finally, this study demonstrates that β2-adrenoceptor ligands play an important role in blood leukocyte deactivation to LPS after hemorrhagic shock.