Received for publication, November 20, 1996 ƒ¿-Elastin with an average molecular mass of 70kDa, an oxalic acid fragmentation product of highly purified insoluble elastin, induced the migration of macrophages, with maximum activity at 10-1ƒÊg/ml. Relative to the positive control of 10-8M N-formylmethionyl-leu cyl-phenylalanine(fMLP), the responsiveness of macrophages to ƒ¿-elastin was nearly the same. Checkerboard analysis demonstrated that the cell movement is chemotaxis and not chemokinesis. A homologous deactivation test showed the possibility of the existence of ƒ¿-elastin-recognizing sites on macrophages. In connection with macrophage chemotaxis in response to ƒ¿-elastin, the intracellular signaling pathway was examined. The guanosine 3• L, 5• L-cyclic monophosphate(cGMP) level was enhanced in macrophages stimulated by a elastin, whereas the adenosine 3• L, 5• L-cyclic monophosphate(cAMP) level was not. Chemo taxis assaying of macrophages treated with 8-Br cGMP- and dibutyryl cAMP-loaded macrophages indicated that cGMP promotes cell movement and cAMP suppresses cell locomotion. The possible involvement of protein kinases in the ƒ¿-elastin signaling pathway was explored by use of inhibitors specific for cGMP-dependent protein kinase(PKG), cAMP-dependent protein kinase(PKA), protein kinase C (PKC), and tyrosine kinase. The macrophage chemotactic response to ƒ¿-elastin was inhibited by the PKG inhibitor, but not by the PKA, PKC, or tyrosine kinase inhibitor. These results suggested that the increase in the cGMP level and the activation of PKG in macrophages are involved in ƒ¿-elastin-induced macrophage chemotaxis.