The material factors which relate to the degradation and/or leaching of ions or molecules are described and the possible biological pathways which they may activate are described, i.e. cytotoxic, immune, tumor and nonspecific inflammatory response. Cytotoxicity is the only biological response which may be measured with high sensitivity by an in vitro assay prior to implantation. All other biological pathways require some degree of in vivo involvement. Three examples of biological response to material factors associated with devices which require evaluation by in vivo assays are discussed, namely: surface topology (texture), mechanically induced factors at the device/tissue interface caused by differences in compliance, and dystrophic calcification in connective tissue and vascular devices.