Electrode fouling and biocompatibility problems remain the greatest obstacles to developing a stable glucose sensor for continuous in vivo monitoring in whole blood. Nafion encapsulation successfully prevents electrode fouling, and substantially inproves the stability and performance of whole blood and plasma glucose sensors in vitro. Results are presented which indicate that Nafion also provides a biocompatible interface with the body, and hence offers the potential for use with implantable sensors. A biocompatible enzyme electrode system is proposed, based on Nafion polymer encapsulation, which has a suitable size and geometry to be tested as an implantable sensor for long-term use. A custom-designed CMOS integrated potentiost was used to evaluate the electrode response in whole blood.