Physical and chemical properties of the surfaces of implants are of considerable interest for dental and orthopedic applications. We used self-assembled monolayers (SAMs) terminated by various functional chemical groups to study the effect of surface chemistry on cell behavior. Cell morphology and proliferation on silicon wafers of various roughnesses and topographies created by chemical etching in caustic solution and by corundum sandblasting were analyzed as well. Water contact angle data indicated that oxidized wafer surfaces displayed high hydrophilicity, modification with poly(ethylene glycol) (PEG) created a hydrophilic surface, and an amino group (NH2) led to a moderately wettable surface. A hydrophobic surface was formed by hydrocarbon chains terminated by CH3, but this hydrophobicity was even further increased by a fluorocarbon (CF3) group. Cell proliferation on these surfaces was different depending primarily on the chemistry of the terminating groups rather than on wettability. Cell proliferation on CH3 was as high as on NH2 and hydrophilic oxidized surfaces, but significantly lower on CF3. Precoating of silicon wafers with cell culture serum had no significant influence on cell proliferation. Scanning electron microscopy indicated a very weak initial cell-surface contact on CF3. The cell number of osteoblasts was significantly lower on sandblasted surfaces compared with other rough surfaces but no differences were detected with 3T3 mouse fibroblasts. The different surface roughnesses and topographies were recognized by MG-63 osteoblasts. The cells spread well on smooth surfaces but appeared smaller on a rough and unique pyramid-shaped surface and on a rough sandblasted surface.