Monocyte chemoattractant protein-1 (MCP-1) is important for both integrin activation and cell migration during the chemotactic response of monocytes. Although these two processes are closely connected, the signaling pathways associated with each have not been well defined. Ashida et al. show that different mitogen-activated protein kinase (MAPK) pathways are required in each process. Inhibition of p38 MAPK inhibited chemotaxis, whereas ERK (extracellular-regulated kinase) inhibition greatly reduced integrin activation, as measured by adhesion to fibronectin. Additionally, inhibiting the function of Rho or Rho kinase also blocked migration but not integrin activation. Although the biochemical signaling point at which both MCP-1-dependent pathways diverge has not been identified, the elucidation of specific proteins involved in migration and integrin activation should help clarify these signaling pathways.