Enterovirus 71 is a picornavirus associated with fatal neurological illness in infants and young children. Here we report the crystal structure of enterovirus 71 and show that, unlike in other enteroviruses, the "pocket factor," a small molecule that stabilizes the virus, is partly exposed on the floor of the canyon. Thus the structure of antiviral compounds may require a hydrophilic head group designed to interact with residues at the entrance of the pocket.