CD134 (OX40) is a member of the tumor necrosis factor (TNF) receptor superfamily expressed on activated T cells. Here, we show that human peripheral blood neutrophils express CD134. Activationof CD134 by soluble CD134 ligand (OX40 ligand/gp34) resulted in delayed caspase-3 activation and consequently in delayed neutrophil apoptosis in vitro. Moreover, CD134 ligand, like G-CSF, maintained anti-apoptotic Mcl-1 levels and inhibited cleavage of the pro-apoptotic Bcl-2 family members Bid and Bax in these cells, suggesting that CD134-mediated signals block apoptosis pathways proximal to mitochondria activation. In conclusion, CD134 regulates neutrophil survival, suggesting that this molecule does not only contribute to adaptive but also to innate immune responses.