A blend of Silastic 382 (Room Temperature Vulcanizing, RTV) Medical Grade silicone oil and a catalyst was prepared in vitro, in both the catalyzed and noncatalyzed state, and injected subcutaneously in mice, rats, and rabbits. When properly blended, this catalyzed material, referred to as "silicone gel," formed a soft rubbery mass that remained at the site of injection. Properly catalyzed silicone rubber gel produces no macroscopic inflammatory reaction, attracts few polymorphonuclear leucocytes, and after 5-6 days a thin fibrous capsule begins to form aroung the gel. No degeneration of the silicone gel was observed during the 62 days of this experiment. Additional rats with this silicone gel have been under observation for 8 months and clinically have shown no changes in the local mass of silicone. If the catalyst is partly oxidized when added to the silicone fluid, the degree of gelling is much less. A local mass usually forms at the site of injection with some of the fluid diffusing into the tissue, forming minute cysts. The inflammatory reaciton is characterized by polymorphonuclear leucocytes, associated with many macrophages and giant cells phagocytizing oil droplets and particles of the diatomaceous earth. The pathogenesis of the inflammatory reaction is discussed, referring to the ionic change and the emigration of polymorphonuclear leucocytes to particles of plastics embedded in tissue.