A secondary structure model for the 5′ non-coding RNA of poliovirus has been derived by comparing computer-generated folding patterns of equivalent sequences from a number of related enteroviruses and rhinoviruses and identifying compensating mutations that suggest conservation of a common secondary structure. Although certain elements are similar, the new model differs considerably from a previously published minimal energy structure and is consistent with the observed sensitivity of in vitro RNA transcripts of infectious poliovirus cDNA to RNases and modifying chemicals. The sequence of a neurovirulent revertant of an attenuated mutant provides additional evidence for an interaction between a region known to be important for neurovirulence, sequence 471–483, and nucleotides 528 to 538.