Enterovirus 71 (EV71) is capable of causing paralytic disease indistinguishable from poliomyelitis due to poliovirus. To determine the relationship of EV71 to poliovirus and other enteroviruses, two strains of EV71 have been cloned and sequenced. The EV71 strains had only 46% amino acid identity with the polioviral P1 capsid region and 55% with the entire polyprotein. There were no regions of high similarity that might account for their respective ability to cause paralytic disease. The two strains, a neurovirulent isolate (EV71/7423/MS/87) and the prototype strain (EV71/BrCr), share 81% nucleotide identity and 95% amino acid identity. Sequence comparisons in the coding region between the two EV71 strains and other picornaviruses indicate that EV71, coxsackievirus A16 and coxsackievirus A2 comprise a distinct genetic group within the enteroviruses.