Hepatitis A virus (HAV) is a hepatotropic member of the family Picornaviridae. Currently, the entire nucleotide sequence is available for only 26 HAV isolates. The complete genome sequence of genotype IA HAV from strains isolated in South America, where genotype IA is the most prevalent genotype, remains unknown. In this study, the complete nucleotide sequence was determined for a genotype IA HAV isolate recovered from a Uruguayan patient (HAV5). Phylogenetic analysis performed using HAV5 and all available full-length IA genotype HAV strains revealed a high synonymous substitution rate throughout the HAV polyprotein. The results of these studies revealed strong selection against amino acid replacements along the HAV polyprotein and may explain, at least in part, the presence of a single HAV serotype.