Biodegradable poly(phosphoesters) with varying side group chemistry and copolymers of styrene and methyl vinyl ketone (MVK) with varying degrees of hydrophobicity were used to study the growth and behavior of surface-attached fibroblasts and hepatocytes. Mouse 3T3 fibroblasts and chicken embryo fibroblasts attached and proliferated on all of the polymers tested. Fewer cells attached to copolymers of styrene and MVK than to glass or tissue culture polystyrene controls; cell attachment to several poly(phosphoester) surfaces was indistinguishable from controls. The mean speed of fibroblast migration was faster on surfaces where fewer cells attached (59 to 84 microns/h on low attachment surfaces compared with 40 to 46 microns/h on high attachment surfaces). When surface-attached cells were stained with fluorescently labeled phalloidin, only a fraction of the cells on low attachment surfaces were shown to have prominent arrays of actin filament bundles. Chicken hepatocytes also attached to the polymer surfaces. When a suspension containing a large number of cells was placed over the polymer surfaces, approximately 50% of the hepatocytes attached during the first 9 h. Surprisingly, hepatocyte attachment and viability in culture were relatively insensitive to the chemistry of the synthetic polymer substrates. Cell number increased by about a factor of 2 over the first 48 h of culture, then decreased back to approximately 50% of initial cell number over the next several days. Cell morphology did depend on the chemical structure of the substrates.