We studied proliferative responses of bovine T lymphocytes to foot-and-mouth disease virus (FMDV) serotypes A, O and C as well as to three peptides including the two major B-cell epitopes of FMDV (VP1[141-156] and VP1[200-213]). Peripheral blood mononuclear cells (PBMC) from cattle previously vaccinated with monovalent vaccine responded to both homotypic and heterotypic virus strains. Of 14 FMDV-specific bovine T-cell clones, which were prepared from PBMC of an animal vaccinated with the trivalent vaccine, 11 reacted to each of the three serotypes A, O and C. This indicates that several T-cell epitopes might be conserved among these serotypes. PBMC from one of two cattle immunized with VP1[141-156]KLH, one of two cattle immunized with VP1[200-213]KLH and two of three cattle immunized with CC-VP1[200-213]-PPS-VP1[141-156]-PCG responded to the homotypic virus strain. After immunizations with VP1[200-213]KLH also heterotypic responses were found. Thus, it appears that these two B-cell sites include T-cell determinants that are recognized by some cattle. However, when proliferative responses of PBMC from an animal vaccinated with the trivalent vaccine were tested, no responses were found to VP1[141-156] and VP1[200-213], whereas the response was very poor to CC-VP1[200-213]-PPS-VP1[141-156]-PCG. These results suggest that these sequences do not represent dominant T-cell epitopes and/or that T-cell reactivity towards these synthetic peptides does not completely cover the T-cell reactivity towards the fragments present after processing of the whole virus.