Neutral endopeptidase (NEP; EC 3.4.24.11) efficiently hydrolyses many neuropeptides. To determine the distribution of NEP, a possible regulatory enzyme for the neuropeptide-induced leukocyte activation, among human leukocytes, we investigated the enzymatic activity of NEP in each cell type of human peripheral blood leukocytes. The activity of NEP assessed by an NEP inhibitor phosphoramidon-sensitive Met5-enkephalin degrading activity was present in neutrophils (59.0 +/- 9.1 pmol/min 10(6) cells); however, the NEP activity was virtually absent in mononuclear cells, eosinophils and basophils. Common acute lymphoblastic leukemia antigen (CALLA) detected immunocytochemically with three anti-CALLA antibodies, whose amino acid sequence has been shown to be identical with that of NEP, was also found only in neutrophils, but not in other blood leukocytes. It is suggested that NEP might regulate the neuropeptide-induced activation of human neutrophils.