Non-structural as well as VP1 recombinant proteins of foot-and-mouth disease virus (FMDV) produced in E. coli, have been used to study the specific antibody response of infected or vaccinated swine. An analysis of sera from infected pigs, using a direct ELISA, showed that polypeptide 3ABC (spanning non-structural proteins 3A, 3B and 3C) was the most antigenic among the recombinant proteins studied and allowed specific detection of FMDV infected swine from the second week after the infection. The sensitivity of this assay was comparable to that obtained when the whole FMDV was used as ELISA antigen. Conversely, use of polypeptide 3ABC did not allow detection of significant levels of antibodies in sera from vaccinated animals. This differential pattern of ELISA reactivities offers a promising approach for the distinction of infected from vaccinated pigs. In addition, a highly specific and sensitive method of diagnosis for FMDV replication was achieved using an immunoblotting assay which detected antibodies against the 3ABC polypeptide.