The effects of the biological environment on the perfluorosulfonated ionomer Nafion membrane were investigated. Nafion membranes thermally annealed at 120°C and kept in culture medium or implanted subcutaneously in rats showed extensive cracking after 4 weeks. In membranes annealed at 150°C, cracking was reduced, but not eliminated. Deposits of calcium phosphates in the membrane were identified. These deposits appeared to be responsible for the cracking of the membranes, but the precise mechanism was unclear.The permeability to glucose of Nafion membranes annealed at 120°C increased at 1 week and then decreased during the 3 following weeks. However, the cracking, protein adhesion, and mineralization of the membranes made the results difficult to interpret.This study revealed that mineralization of Nafion occurs in the biological environment, resulting in cracking and changes in permeability. Modifications to prevent the mineralization of Nafion are necessary to make it suitable for use in the implantable glucose sensor.