Poliovirus is the etiological agent of poliomyelitis. From the observations that only simians are susceptible to poliovirus infection and that 37 amino acid sites (the poliovirus-binding associated [PBA] sites) in the domain D1 of CD155 are involved in the binding to poliovirus, it is considered that the susceptibility to poliovirus infection evolved through amino acid substitutions that occurred at the PBA sites on the ancestral branch of simians. Here it is shown that positive selection has operated on these substitutions by analyzing the nucleotide sequences encoding almost the entire region of D1 in humans, non-human hominoids (chimpanzees and gorillas), Old World monkeys (African green monkeys), New World monkeys (brown capuchins, squirrel monkeys, and marmosets), prosimians (ring-tailed lemurs), and non-primate mammals (rabbits). Positive selection is unlikely to have operated on the susceptibility to poliovirus infection, but possibly on the binding to another molecule. Elimination of susceptibility to poliovirus infection in simians may be difficult, because it also requires elimination of advantageous effects that have been exerted by CD155.