We have determined the crystal structure of the proteolytic component of the caseinolytic Clp protease (ClpP) from E. coli at 2.3 Å resolution using an ab initio phasing procedure that exploits the internal 14-fold symmetry of the oligomer. The structure of a ClpP monomer has a distinct fold that defines a fifth structural family of serine proteases but a conserved catalytic apparatus. The active protease resembles a hollow, solid-walled cylinder composed of two 7-fold symmetric rings stacked back-to-back. Its 14 proteolytic active sites are located within a central, roughly spherical chamber ∼51 Å in diameter. Access to the proteolytic chamber is controlled by two axial pores, each having a minimum diameter of ∼10 Å. From the structural features of ClpP, we suggest a model for its action in degrading proteins.