An implantable 0.29 mm o.d. flexible wire electrode was designed for subcutaneous monitoring of glucose. The electrode was formed by sequentially depositing in a 0.09 mm deep shielded recess at the tip of a polyimide-insulated 0.25 mm gold wire a "wired" glucose oxidase (GOX) sensing layer, a mass transport limiting layer, and a nonfouling biocompatible layer. The glucose sensing layer was formed by cross-linking (poly[(1-vinylimidazolyl)osmium(4,4'-dimethylbipyridine)2Cl] )+/2+(PVI13-dme - Os) and GOX with poly(ethylene glycol) diglycidyl ether (PEG). The glucose mass transport restricting layer consisted of a poly(ester sulfonic acid) film (Eastman AQ 29D) and a copolymer of polyaziridine and poly(vinyl pyridine) partially quaternized with methylene carboxylate. The outer biocompatible layer was formed by photo-cross-linking tetraacrylated poly(ethylene oxide). The three layers contained no leachable components and had a total mass less than 2.2 micrograms (approximately 50 ng of Os). When poised at +200 mV vs SCE and operated at 37 degrees C, the 5 x 10(-4) cm2 electrode had in vitro a sensitivity of 1-2.5 nA mM-1. The current increased with the glucose concentration up to 60 mM, and the 10-90% response time was approximately 1 min when the glucose concentration was abruptly raised from 5 to 10 mM. The sensitivity decreased by less than 4% over a test period of 1 week, during which the electrode was operated continuously in a 10 mM glucose physiological buffer solution at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)