Secretoneurin (SN), a novel neuropeptide, specifically induces the selective chemotactic migration of monocytes in vitro and in vivo. Mediation of the migratory effects by yet unidentified receptors for secretoneurin is likely. Whether phagocytes other than monocytes are targets of SN's action, is currently unknown. Since previous data suggested that SN does not induce chemotaxis of neutrophils, we tested SN priming for respiratory burst activity, adherence to endothelial cell (EC) monolayers and effects on chemoattractant-stimulated migration of neutrophils. We found that priming of neutrophils with SN fails to enhance triggered respiratory burst activity or adherence to EC as compared to tumor necrosis factor-alpha (TNF), a well-known neutrophil-priming cytokine. Pretreatment, however, revealed an increase in spontaneous locomotion, and significant antagonism of formylpeptide (FMLP)-stimulated migration of neutrophils in modified Boyden chamber assays. The latter effect was similar to inhibition of FMLP-stimulated chemotaxis by TNF. The effects of SN on neutrophil migration could be abolished by an antiserum to SN, indicating its specificity. Data show that in vitro neutrophils are specifically affected by SN possibly by activation of a priming-type receptor. Since neutrophils represent a valuable tool for receptor research, further studies on SN receptors of leukocytes may be performed on these cells.