Neutrophil apoptosis is a constitutive process that can be enhanced or delayed by signals induced by various stimuli. We investigated the role of phospholipase D (PLD) in neutrophil apoptosis. The apoptotic rate of neutrophils was found to be increased by 1-butanol and decreased by the exogenous addition of PLD. Moreover, the delay of apoptosis by apoptosis-delaying stimuli such as granulocyte/macrophage colony-stimulating factor or lipopolysaccharide (LPS) was also blocked by 1-butanol. Unstimulated PLD activity in cultured cells for 20 h was higher than that in freshly isolated cells and further increased in cultured cells with LPS. These results suggest that PLD is involved in the up-regulation of neutrophil survival.