Abstract: Numerous studies have provided evidence that fibrinogen plays a multifaceted role in the immune and inflammatory response. The ability of fibrinogen to participate in the inflammatory response depends on its specific interaction with leukocyte cell surface adhesion receptors, integrins. Two leukocyte integrins, αMβ2 (CD11b/CD18, Mac-1) and αXβ2 (CD11c/CD18, p150,95), are the main fibrinogen receptors expressed on neutrophils, monocytes, macrophages and several subsets of lymphocytes. The recognition site for αMβ2 has been previously mapped to the carboxyl-terminal globular γC domains (γ143–411) and two sequences, γ190–202 (P1) and γ377–395 (P2), were implicated as the putative binding sites. We now demonstrate that a second leukocyte integrin, αXβ2, which is highly homologous to αMβ2, mediates adhesion of the αXβ2-bearing cells to the D fragment and to the recombinant γ-module, γ143–411. Within the γC domain, αXβ2 may recognize P1 and P2 sequences since synthetic peptides duplicating these sequences effectively inhibits adhesion of the αXβ2-expressing cells to the D fragment. In addition, neutrophil inhibitory factor, NIF, a potent inhibitor of αXβ2, also inhibited αXβ2-mediated cell adhesion. These data suggest that recognition of the γC domain of fibrinogen by αMβ2 and αXβ2 may have common structural requirements.