The effect of specific chemical functionalities on the growth of bovine aortic endothelial cells (BAEC) was investigated using a set of well-characterized, chemically functionalized surfaces prepared by self-assembly of alkanethiolate monolayers on gold surfaces using the molecules X(CH2)(15)SH with X = -CH3, -CH2OH, -CO2CH3, and -CO2H. Cells seeded on a substrate in serum-containing culture medium interact with the adsorbed protein layer rather than the substrate. Therefore, the role of two serum proteins, albumin (Alb) (a nonadhesive or blocking protein) and fibronectin (Fn) (an adhesive protein), in cell growth was evaluated by measuring the amount of each protein bound and the tightness of binding (determined by resistance to SDS solubilization) on the self-assembled monolayers (SAMs). BAEC growth varied significantly with surface functionality. Cell growth increased in the following order : -CH2OH < -CO2CH3 < -CH3 much less than -CO2H, illustrating the effect of specific surface groups. Cell growth on all monolayer surfaces was lower than on tissue culture polystyrene suggesting that multiple chemical functionalities may be desirable for cell growth. Protein interaction studies demonstrated variations in protein adsorption and elutability in response to the SAM terminal functional group. Alb adsorption and Fn elutability did not differ significantly with terminal functional group. The best cell growth substrate (COOH SAM) demonstrated significantly higher Fn adsorption and Alb elutability than did the poor growth substrates (CO2CH3 and OH SAMs).