Molecular cloning techniques have provided new information on the organization of the picornavirus genome and increased reader understanding of the function of many of the nonstructural proteins. The viral RNA acts both as a message for translation of new viral protein and as the template for replication of negative-strand RNA, which in turn serves as the template for replication of virion RNA. Since the picornavirus genome resembles eukaryotic messenger RNA, techniques developed for transcribing mRNAs into cDNA have been useful for molecular cloning. More acceptable experiments may involve the use of eukaryotic expression systems in which HAV infection could be complemented. In the capsid-coding region, analysis of the nucleotide and amino acid sequences leads to some very interesting predictions. Molecular biology, X-ray crystallography, and other techniques of modem virology combined with improved biologic and serologic systems will continue to reveal the nature of this interesting, unusual and important picornavirus.