In order to study the biocompatibility of metal electrodes and insulations in the rat brain, eight different metal electrode types and two different insulations were implanted for 11, 35, 36, 37, or 63 days. Stainless steel and Nichrome were nontoxic metals, silver was toxic, and copper extremely toxic with phagocytosis active to 37 days of implantation. Active phagocytosis was easily detected by high glucose demand using 2-deoxy[14C]glucose (2-DG) autoradiography contrasted with normal 2-DG autoradiographs where phagocytes were present but not ingesting. Epoxylite, an epoxy-polyester varnish, was slightly more reactive in brain than polyimide but not statistically significant. In general, larger electrodes created more tissue reaction per se for as long as 37 days. These results suggested that a thin stainless-steel bipolar electrode will provide safe recording electrodes in either animal or human brain. The importance of these findings is that certain metals (silver, copper) cannot be used in the brain without producing necrosis and phagocytosis, whereas other metals (stainless steel, Nichrome) with varnish insulators (Epoxylite, polyimide) can be implanted without producing any detectable damage beyond that of the initial trauma and brief phagocytosis limited to the edge of the electrode track. Finally, the glucose metabolism autoradiographs differentiated active phagocytosis (copper) from inactive phagocytes (silver) when using long implants (37 days) of toxic metals.