The widespread use of marker vaccines and diagnostic approaches able to differentiate infected from vaccinated animals (DIVA), has led to the elimination of PRV from domestic swine populations in many countries. Nevertheless, the PRV continues to circulate in global feral swine populations and is occasionally introduced into commercial herds. More concerning, since 2011, a highly pathogenic PRV variant has spread across swine production systems in China. Given these circumstances, PRV remains an important transboundary swine disease.The general objective of this dissertation was to establish a DIVA-compatible PRV diagnostic approach using swine oral fluid, rather than serum. In Chapter Three, the detection of PRV gB DNA in oral fluid specimens was evaluated using an established quantitative real-time PCR (qPCR) and samples of known PRV infection status. PRV gB DNA was detected in oral fluid specimens from PRV-inoculated animals with a pattern similar to nasal swabs. Thereafter, the detection of PRV antibodies in oral fluids was explored (Chapter Four) by adapting a commercial PRV whole-virus indirect ELISA to oral fluid specimens. PRV antibody responses were detected as early as 14 days post inoculation in PRV-inoculated animals. Finally, a DIVA approach to PRV diagnosis was tested (Chapter Five) by evaluating the detection of PRV gE IgG in oral fluid specimens using a recombinant gE dual matrix indirect ELISA. Significant gE IgG responses were detected in oral fluid specimens from PRV-inoculated pigs, with similar timing to the whole-virus PRV antibody response described in Chapter Four. In conclusion, the successful detection of PRV viral DNA and antibodies suggests that oral fluid specimens could be used for the differentiation of naïve, acutely infected, vaccinated, and infected animals. That is, the core components of PRV monitoring, control, surveillance, and eradication could be met using oral fluids collected from swine in commercial herds.