To identify foot-and-mouth disease virus (FMDV) specific T-cell epitopes within the entire polyprotein sequence of the virus, 442 overlapping pentadecapeptides were tested in proliferation assays using lymphocytes from cattle experimentally infected with FMDV. Four months post-infection cells from all investigated animals (n = 4) responded by proliferation and interferon-gamma production to a peptide located on the structural protein 1D (VP1), amino acid residues 66-80. Major histocompatibility complex (MHC) serotyping of the investigated cattle indicated that all animals shared the MHC serotype A31 which comprises the class II allele DRB3 0701. This may explain the common recognition of this newly discovered epitope. Responses to other peptides could only be observed in one animal and rapidly declined during the time course of the study. These observations point to an immunodominant role of this epitope located on the protein 1D in cattle with MHC serotype A31.