We have determined the complete nucleotide sequence of coxsackievirus A21 (CAV-21), the first member of this enterovirus subgroup to be analysed in molecular detail. The sequence, which is 7401 nucleotides long, encodes an open reading frame of 2206 codons, preceded by a 5' non-coding region of 711 nucleotides and followed by a 3' non-coding region of 72 nucleotides plus a poly(A) tract. The most striking feature is the remarkable homology to the poliovirus (greater than 90% at the amino acid level) in the 3' part of the genome. The rest of the genome is much less homologous, suggesting that CAV-21 is a recombinant virus. Rhinovirus-like characteristics, including the length of the 5' non-coding region and a slight --U/--A imbalance in codon usage, may be related to the fact that CAV-21, like rhinoviruses, infects the upper respiratory tract. However, the sequence sheds little light on the molecular basis of the shared receptor specificity.