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, α_Mβ₂ (CD11b/CD18, Mac‐1) and α_Xβ₂ (CD11c/CD18, p150,95), are the main fibrinogen receptors expressed on neutrophils, monocytes, macrophages and several subsets of lymphocytes. The recognition site for α_Mβ₂ 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, α_Xβ₂, which is highly homologous to α_Mβ₂, mediates adhesion of the α_Xβ₂‐bearing cells to the D fragment and to the recombinant γ‐module, γ143–411. Within the γC domain, α_Xβ₂ may recognize P1 and P2 sequences since synthetic peptides duplicating these sequences effectively inhibits adhesion of the α_Xβ₂‐expressing cells to the D fragment. In addition, neutrophil inhibitory factor, NIF, a potent inhibitor of α_Xβ₂, also inhibited α_Xβ₂‐mediated cell adhesion. These data suggest that recognition of the γC domain of fibrinogen by α_Mβ₂ and α_Xβ₂ may have common structural requirements.