Adhesion is required for cell growth, differentiation, survival, and function. Cell adhesion is mediated by a structurally diverse group of plasma membrane receptors, each exhibiting specialized ligand-binding properties that are needed for specific tasks. Integrin-mediated adhesion is important for hematopoietic stem (HSC)/progenitor (HPC) cell survival and may prevent programmed cell death. Interleukin (IL)-11, a multi-functional cytokine secreted by the bone marrow environment, plays an important role in regulating growth and differentiation of HSCs/HPCs. In this report, we demonstrate that IL-11 enhanced adhesion of freshly isolated and 3 day-expanded CD34+ cells to immobilized fibronectin. the expression of very late antigen (VLA)-4 and VLA-5 integrins was detected on CD34+ cells. CD34+ cells also expressed a-chain and gp130 subunits of the IL-11 receptor (R). Enhanced adhesion by IL-11 was mediated via activation of VLA-5 integrins, since this action could be blocked by monoclonal antibodies against beta 1 and alpha 5, but not alpha 4, integrins. Addition of phosphatidylinositol (PI)-3 kinase inhibitors blocked IL-11 enhanced adhesion of CD34+ cells to fibronectin. The results suggest that this enhanced adhesion is associated with the PI-3 kinase pathway, an inside-out signaling pathway.