A phylogenetic tree relating the VP1 gene of 15 isolates of foot-and-mouth disease virus (FMDV) of serotypes A, C, and O has been constructed. The most parsimonious tree shows that FMDV subtypes and isolates within subtypes constitute sets of related, nonidentical genomes, in agreement with a quasispecies mode of evolution of this virus. The average number of nucleotide replacements per site for all possible pairs of VP1 coding segments is higher among representatives of serotype A than serotype C or O. In comparing amino acid sequences, the values of dispersion index (variance/mean value) are greater than 1, with the highest values scored when all sequences are considered. This indicates an accumulation of mutations at a limited number of residues, suggesting that distributions of sequences fluctuate around points of high stability. Evolution of FMDV follows a path very distant from that of a star phylogeny, and it has not been possible to derive conclusions on constancy of evolutionary rates with the test applied to the analysis. FMDVs, as other RNA viruses, are of limited genetic complexity and their population sizes are extremely large. Their evolution concerns complex, indeterminate mixtures of genomes rather than a single, determinate species.