The aims of this study were to investigate the effects of Interleukin-8 (IL-8) and Growth related oncogene-⍺ (Gro-⍺) on neutrophil apoptosis and determine the potential for a selective CXCR2 antagonist to inhibit these responses. IL-8 and Gro-⍺ both produced dose dependent inhibition of spontaneous human neutrophil apoptosis after 16 hours incubation (59±3.5% and 27.5±3% respectively; EC50s 2.2±1.8nM, and 0.5±0.2nM respectively). The pro-survival effect of a fixed concentration of agonist (IL-8 or Gro-⍺) on cultured neutrophils was abrogated by a selective CXCR2 antagonist SB272844 (K_Ds 253nM and 49.9nM in the presence of IL-8 or Gro-⍺ respectively). Our data suggests that the anti-apoptotic effect of Gro-⍺ is mediated through CXCR2 as selective CXCR2 blockade with SB272844 can potently abrogate this response. The inhibitory effect of IL-8 may in addition partly be mediated through CXCR1 as SB272844 was less potent in its ability to abrogate the anti-apoptotic effects of IL-8 when this agent was used as an agonist. CXCR2 antagonists may have a therapeutic role in controlling neutrophil-driven inflammation by reducing neutrophil recruitment and restoring neutrophils to the tissue clearance pathway of apoptosis.