In this study we investigated the epitope-specific antibody response against glycoprotein E (gE) of pseudorabies virus. Epitope-specific antibody responses were investigated by enzyme-linked immunoperoxidase monolayer assays. In a vaccinated crossbred pig population, most pigs responded to antigenic domain E and to a lesser degree to antigenic domains C and D. Only few pigs responded to antigenic domains F, A, and B. Using vaccinated pigs, we investigated the influence of two different pseudorabies virus strains and the genetic background of the host on the epitope-specific antibody response. More pigs infected with the virulent NIA-3 strain had a detectable antibody response against antigenic domains C, F and A than did pigs infected with the mildly virulent Sterksel strain (P < or = 0.05; Fisher's exact test). No differences in the epitope-specific antibody responses of two genetically different pig breeding lines were observed (P > or = 0.1; Fisher's exact test). In both breeding lines the incidence of the epitope-specific antibody response was comparable to that in the crossbred pig population. In addition, we studied the epitope-specific antibody responses were strikingly different and indicated that genetic background influenced the epitope-specific antibody response. Of the serum samples of mice with C57BL and a BALB background, 40 and 17% respectively, were positive in the one of the epitope-specific immunoassays. In contrast to pigs, mice responded predominantly to antigenic domain D and to a lesser degree to antigenic domains E and B. Only few mice had a detectable antibody response against antigenic domains C and A, and none had a detectable antibody response against antigenic domain F.