The neuropeptide galanin is widely distributed in the central and peripheral nervous systems and mediates its effects via three G-protein-coupled receptors (GAL1-3 receptor). Galanin has been shown to be involved in different inflammatory processes.1 A key event in inflammation is the recruitment of circulating leukocytes into the damaged tissue. In an in vivo rat model of acute arthritis local administration of galanin to inflamed knee joints caused a dose-dependent increase in leukocyte rolling velocity and adhesion within the synovial microvasculature. The effects could be blocked by co-administration of the selective GAL3 receptor antagonist SNAP 37889, indicating an involvement of the GAL3 receptor. Quantitative RT-PCR analysis of the galanin system in isolated human immune cells revealed that Galanin mRNA is expressed in primary human natural killer cells, skin mast cells, monocyte derived macrophages and T/B lymphocytes, whereas GAL1-3 receptors are differentially expressed in various types of immune cells. To elucidate if galanin can directly modulate immune cell function, we treated isolated polymorphonuclear neutrophils (PMNs) and natural killer (NK) cells with galanin. Galanin per se did not influence the activation of PMNs and NK cells, but galanin was able to substantially enhance the sensitivity of PMNs and NK cells towards different cytokines and chemokines. Our data indicate that galanin operates as immune modulator, which does not exert an effect on immune cells on its own, but can regulate the response to other stimuli enhancing or repressing their signaling. Funding: Austrian Research Promotion Agency (822782/THERAPEP).