We describe B-cell linear epitopes detected by Pepscan in the Nsp2 and all of the structural proteins of a US PRRSV strain, using sera of 15 experimentally infected pigs. The Nsp2 was found to contain the highest frequency of immunodominant epitopes (n = 18) when compared to structural proteins. Ten of these 18 Nsp2 peptides were reactive with 80 to 100% of the examined sera. In the structural proteins, epitopes consistently recognized by immune sera were located at gp2 (n = 2), gp3 (n = 4), gp5 (n = 3), M (n = 2) and N (n = 2). Overall, the highest degree of immunogenicity and conservation was exhibited by two epitopes identified in the C-terminal end of the M protein (ORF6). The antibodies recognizing the immunodominant epitopes of each protein were detected as early as days 7 to 15 pi and remained detectable until the end of the experiment (day 90 pi). These findings have direct implications for PRRSV differential diagnostics and eventual eradication as the identified epitopes may represent serologic marker candidates for differential (DIVA) PRRSV vaccines, derived from infectious cDNA clones.