Self-assembled monolayers (SAMs) of alkanethiols, which can provide flat and chemically well-defined surfaces, were employed as model surfaces to understand cellular interaction with artificial materials. SAMs presenting a wide range of wettabilities were prepared by mixing two kinds of alkanethiols carrying terminal methyl (CH(3)), hydroxyl (OH), carboxylic acid (COOH), or amino (NH(2)) groups. Adhesion behavior of human umbilical vein endothelial cells (HUVECs) and HeLa cells on these mixed SAMs were examined. The number of adhered HUVECs reached a maximum on CH(3)/OH mixed SAMs with a water contact angle of 40 degrees , while cell adhesion increased with decreasing water contact angle up to 60-70 degrees and then leveled off on CH(3)/COOH and CH(3)/NH(2) mixed SAMs. Numbers of adhered HeLa cells showed a maximum on CH(3)/OH and CH(3)/COOH mixed SAMs with a water contact angle of 50 degrees . These facts suggest that cell adhesion is mainly determined by surface wettability, but is also affected by the surface functional group, its surface density, and the kinds of cells. The effect of exchange of adsorbed proteins on cell adhesion was also examined. HUVECs were cultured on the mixed SAMs preadsorbed with albumin. Cell adhesion was effectively prohibited on hydrophobic SAMs pretreated with albumin. Albumin strongly adsorbed and resisted replacement by cell adhesive proteins on hydrophobic SAMs. On the other hand, cells adhered to albumin-adsorbed hydrophilic SAMs. Displacement of preadsorbed albumin with cell adhesive proteins effectively occurs on these hydrophilic SAMs. This effect contributes to induce SAMs with moderate wettability to give suitable surfaces for cell adhesion.