To improve the cell compatibility of poly(L-lactide-co-glycolide) (PLGA; 75/25 molar ratio of lactide to glycolide) surfaces, we experimented with physicochemical treatments. Chemical treatments employed 70% chloric acid, 50% sulfuric acid, and 0.5N sodium hydroxide solutions, and physical methods included corona and plasma treatments. The water contact angle of surface-treated PLGA decreased from 73 to 50-60degrees; that is, the hydrophilicity increased because of the introduction of oxygen-containing functional groups onto the PLGA backbone according to electron spectroscopy for chemical analysis. The physicochemically modified PLGA surfaces were used to investigate the interaction of four different types of cells-hepatoma (Hep G2), osteoblast (MG 63), bovine aortic endothelial (CPAE), and fibroblast (NIH/3T3) cells-in terms of the surface hydrophilicity and hydrophobicity of PLGA. The cells that adhered and grew on the physicochemically modified PLGA surfaces were counted and observed with scanning electron microscopy. The adhesion and growth of Hep G2, MG 63, CPAE, and NIH/3T3 cells on physicochemically treated PLGA surfaces, especially on chloric acid-treated PLGA surfaces, were more active than on the control. This result seems closely related to the serum protein adsorption on the surface; the serum proteins were also adsorbed more on the hydrophilic surface. Surface hydrophilicity apparently plays an important role in cell adhesion, spreading, and growth on PLGA surfaces. The surface modification technique used in this study may be applicable to tissue engineering for the improvement of tissue compatibility of film- and scaffold-type substrates.