Surveys for evidence of exposure to pseudorabies virus (PRV), Brucella suis, swine influenza virus (SIV; human-like H1N1, reassortant type H1N1, H1N2-like H1N1 and H3N2), porcine circovirus 2 (PCV 2), and porcine respiratory and reproductive syndrome virus (PRRSV) in feral swine (Sus scrofa) were conducted in areas where feral swine were geographically associated with high densities of transitional swine premises in South Carolina and high densities of commercial swine production in North Carolina. In South Carolina, 10/50 (20.0%), 7/50 (14.0%), and 29/49 (59.2%) feral swine tested antibody positive for PRV, B. suis, and PCV-2, respectively. Antibodies to PRRSV (0/49) and SIV (0/49) were not detected. In North Carolina, antibodies to PRV and B. suis were not detected in serum samples from 120 feral swine; however, antibodies to PRRSV (1/120 [0.8%]), PCV-2 (86/120 [71.7%]; these included 80 positives plus six suspects), and SIV (108/119 [90.7%]) were present. The presence of PRV and B. suis in South Carolina may have been due to the introduction of infected feral swine into the area or to a previous association of feral swine with infected transitional swine. Their absence in the North Carolina populations may have been due to the absence of these disease agents in the feral swine originally introduced into the area and the lack of a potential for contact with infected commercial swine. Feral swine associated with commercial swine in North Carolina may have been exposed to SIV subtypes circulating in commercial swine via airborne spread of SIV from commercial swine facilities. Feral swine seropositive for PCV-2 were prevalent in both states, which may indicate efficient transmission from commercial swine and transitional swine, or that PCV-2 is widespread in feral swine. The low prevalence of animals with antibodies against PRRSV may indicate a less-than-efficient means of transmission from commercial to feral swine. Additional epidemiologic studies are needed to understand the risks and mechanisms of transmission of disease agents among commercial, transitional, and feral swine, and the role of feral swine as reservoirs of these disease agents.