The success of synthetic polymers as biomaterials depends upon their interfacial properties and resultant interactions with cells and biological fluids in vivo. A useful experimental approach to defining requirements for biocompatibility is to study the mechanisms by which synthetic substrata influence eukaryote cell behaviour in culture. Here we present an overview of the relationships between physical and chemical substratum properties and cell behaviour on a range of synthetic polymers. We relate our results to theories of in vivo tissue compatibility.