Three closely related genes for the small genome-linked protein (VPg) of picornaviruses have been identified by sequence analysis as a tandem repeat in the genome of Foot and Mouth Disease Virus (FMDV), strain O1K. This unusual structure was also found in the genome of strain C1O, belonging to a different FMDV serotype. Predicted biochemical properties of the three VPg gene products are in excellent agreement with the data from protein analysis of a heterogeneous VPg population from a third FMDV serotype, strain A10 (1). Taken together, these data indicate that the VPgs from all three genes function equally well in vivo. This is the first report of a tandem repeat gene in a viral genome.