Hematopoiesis occurs in a complex environment in the medullary cavity in close proximity to stromal cells, fibroblasts, endothelial cells and matrix molecules. Hematopoietic cell interactions in this environment appear to involve both integrin and proteoglycan-mediated cell-cell and cell-matrix interactions. Genetic transduction of hematopoietic stem cells via retroviral vectors has been hampered by low efficiency of gene transfer. Recently, hematopoietic stem cell adhesion to the extracellular matrix molecule fibronectin has been shown to increase transduction of these target cells using retrovirus vectors. The mechanism of increased transduction appears to involve colocalization of virus particles and target cells. These data are reviewed in this paper.