The level of expression of the alpha 5/beta 1 integrin fibronectin receptor (FnR) strongly affects the growth rate of CHO cell tumors in nude mice. Here we report that alpha 5/beta 1 expression also influences the organization of the tumor vasculature. Tumors formed from CHO clones defective in FnR expression have a leaky vasculature that gives them a hemorrhagic appearance. Tumors from wild-type CHO cells, or from FnR-deficient CHO clones transfected with constructs coding for the alpha 5 integrin subunit, have an intact, non-leaky vasculature. In tumors from FnR-deficient cells, the endothelial lining of blood vessels is sparse, and red cells and plasma proteins can be detected in the tumor parenchyma. In tumors from cells expressing the alpha 5/beta 1 FnR, tumor vessels are circumscribed by a lining of von-Willebrand-factor-positive endothelial cells, and blood cells and proteins are confined to the vessel lumina. Thus, the level of expression of the alpha 5/beta 1 FnR in the tumor parenchymal cells can influence the development of tumor vasculature. Since alpha 5/beta 1 is vital to the organization of the extracellular matrix, one possibility is that altered matrix assembly contributes to the defective vascularization seen in alpha 5/beta 1-deficient tumors.