This application requests support to finish the development of long term implantable subcutaneous glucose sensor, the first ever achieved. Phase I research has led to the development of proprietary membrane materials which provide long term signal stability and linearity in the low oxygen tension (30-80 mm Hg) and broad glucose concentration (40-400 mg/dl) environment of subcutaneous tissue. The immobilized enzyme activity of these membrane materials survived in vivo implantation in the peritoneal cavity of rats for over a year. These membranes have been press fitted over an electrochemical sensor, coupled to a radio transmitter, and implanted into the subcutaneous tissue of dogs. Upon IV infusion of glucose or insulin the sensor appropriately tracks glucose for months at a time. This subcutaneous sensor response lags the blood glucose response by approximately 8 minutes. Phase II will refine, optimize, and miniature this prototype sensor. More specifically, the sensor/tissue interface will be better defined, both histologically and in terms of the role played by addition of angiogenesis factor. The sensor itself and its power supply and radio transmitter will be further miniaturized and better packaged. The system for manufacturing this sensor and its components will be further developed and validated. The process of regulatory agency clearance will begin by obtaining data on performance, reliability and longevity. Phase III human subject trials are likely to begin during the latter stages of Phase II.