The complete nuelcotide sequence of foot-and-mouth disease virus (FMDV) O/FRA/l/2001 (bovine isolate) was determined from five cDNA clones covering most of the genome and compared with the British porcine isolate (O/UKG/35/2001) it originated from. Seven substitutions, out of which three resulted in amino acid changes (in the leader protease, 3A protein and 3D RNA-dependent RNA polymerase sequences) were identified and confirmed by direct sequencing of RT-PCR products obtained from in vitro infected cells and skin vesicles of an infected cow. RACE amplification allowed determination of the exact 3' end of the genome. These changes and possibly the unusual 3A substitution between the British and its French derivate may account for the consecutive species shifts.