Neuropeptides are putative mediators of inflammation. At physiological concentrations substance P has been shown to prime polymorphonuclear neutrophil granulocyte (PMN) chemiluminescence (CL). In the present study we show also that both endothelin and neuropeptide Y (NPY), but not calcitonin gene-related peptide (CGRP) are able to prime PMN oxidative metabolism. At similar nanomolar concentrations SP and endothelin (but not NPY) also primed formyl-methionyl-leucyl-phenylalanine (fMLP)-induced rises of cytosolic calcium. On the other hand, NPY caused a direct and dose-related increase of cytosolic calcium concentrations. None of the mentioned neuropeptides primed PMN aggregation or directly induced CL, aggregation or chemotaxis over a wide range of concentrations (1 fM-1 muM).