Several neuropeptides, including gastrin-releasing peptide (GRP), modulate the immune response, specifically lymphocyte chemotaxis. In the present work the effect of GRP on the chemotaxis of murine lymphocytes from different immune locations in both, total leukocyte populations and populations depleted of adherent cells have been studied. Specificity of the GRP effect on chemotaxis using an antagonist of the GRP receptor, as well as the implication of nitric oxide (NO), using inhibitors of NO synthase and donors of NO, were investigated. The effects of GRP stimulating the chemotaxis of lymphocytes from peritoneum, axillary nodes and spleen and decreasing the chemotaxis from thymus were receptor-specific and disappeared in lymphocytes from populations depleted of adherent cells. NO synthase inhibitors blocked the GRP effect on lymphocyte chemotaxis, and this action was reversed in the presence of l-arginine. Thus, the effect of GRP on murine lymphocyte chemotaxis appears to be mediated by NO secreted by adherent cells.