Human and bovine endothelial cells were used in a series of studies examining cell adhesion to extracellular matrix macromolecules. Collagen types I and III, an acetic acid extract of bovine lens capsule basement membrane, laminin, and fibronectin were demonstrated to affect, in varying degrees, cell adhesion, cell growth, and "sprout cell" formation in endothelial cell cultures. All the matrix macromolecules tested promoted endothelial cell adhesion, and the adhesion to the basement membrane extract was blocked by antibodies to fibronectin. When human endothelial cells were grown on defined matrices, the level of serum required for optimum growth was decreased, while bovine endothelium grown on defined matrices did not show sprout cell formation. These data suggest that endothelial cells are able to adhere to a wide variety of connective tissue components and that extracellular matrices significantly influence cell behavior.