The beta 2-integrins expressed on leukocytes play a key role in contributing to integrin-mediated adhesion and subsequent leukocyte responses in numerous pathophysiological conditions (1). Plasma protein fibrinogen participates in inflammatory responses by promoting the accumulation of leukocytes (2,3). The differential regulation of the integrin-mediated adhesion and cytoskeletal changes of monocytes polulations may have relevance to their distinct roles in inflammation. Peripheral blood monocytes despite expressing CD11c, primarily adhered to fibrinogen in a CD11b-dependent manner: 90 % (p<0.001, n=3) of monocyte adhesion was blocked using anti-CD11b. However, culture of monocyte in human serum resulted in a 3.4-fold increase in CD11c expression and participation in adhesion to fibrinogen in co-operation with CD11b, suggesting the elevated CD11c expression in the differentiated monocyte population leads to its involvement in adhesion. Simultaneous treatment with anti-CD11b and anti-CD11c resulted in inhibition of adhesion by 85% (p<0.001, n=3). Although both integrins were involved in adhesion, the cytoskeletal reorganization contributing to an increase in spreading of cultured monocytes on fibrinogen was mediated by CD11b. The adhesion of monocytes to fibrinogen was abrogated upon treatment with the Src family kinase (SFK) inhibitor, PP2. The distribution of CD11c showed significant clustering on cultured monocytes upon adhesion to fibrinogen. The diminished clustering on inhibiting SFK activity indicates an important role for SFK activity in regulating CD11c avidity. We also examine the role of Rac2 in regulating beta 2-integrin dependent adhesion and cytoskeletal changes. The expression of dominant negative Rac2 in monocytes led to changes in cell spreading and formation of actin foci suggesting its involvement in integrin mediated inflammatory responses.