Lipopolysaccharide stimulation of adherent THP-1 cells induces morphological changes that are associated with the reorganization of the actin cytoskeleton. We hypothesized that LPS would also increase THP-1 cell adhesion and sought to determine the signaling mechanisms regulating this response. We show that LPS significantly increases THP-1 cell attachment after 1 h, supporting the idea that LPS can stimulate integrin function. By 4 h however, the number of adherent cells returned to control levels. Importantly, detached cells were determined to be viable by propidium iodide staining, indicating that the increase in cell adhesion was transient. LPS-induced adhesion to fibrinogen- but not fibronectin-coated wells was also transient, suggesting that adhesion reflected beta2 integrin activation. This idea was supported by the fact that LPS-induced adhesion could be blocked by a function-blocking anti-beta2 integrin antibody. Interestingly, the protein tyrosine phosphatase (PTP) inhibitor, phenylarsine oxide, prevented cell detachment. Taken together, these data suggest that LPS-mediated integrin activation is transient and can be regulated by PTP-mediated signaling events.