Cell surface hydrophobicity expression by Candida albicans facilitates a diffuse binding distribution of yeast cells to host tissues ex vivo. One possibility for the receptor site responsible for the binding pattern of hydrophobic cells is the extracellular matrix (ECM). In this study, we evaluated the interaction of hydrophobic and hydrophilic C. albicans with ECM proteins immobilized onto wells of microtitre tissue. Culture plates, and the ability of ECM proteins to block the binding of hydrophobic cells to splenic tissue ex vivo. Hydrophobic C. albicans bound in greater numbers than hydrophilic cells to the immobilized proteins, particularly fibrinogen, fibronectin, collagen type IV and laminin. Similar results were obtained regardless of C. albicans strains or of growth medium. Collagen and fibronectin blocked the binding of hydrophobic cells to the white pulp but not to the marginal zones in splenic tissues when tested with the ex vivo assay. These results suggests that the diffuse binding pattern of hydrophobic cells in the ex vivo assay may be due to their enhanced ability over hydrophilic cells to bind to ECM proteins, particularly fibronectin and collagen type IV.