Isolation of Porcine reproductive and respiratory syndrome virus (PRRSV) from oral fluids was first reported in 1997. The objective of the present study was to determine whether PRRSV and/or anti-PRRSV antibodies were present in oral fluids at diagnostic levels. The level and duration of PRRSV and anti-PRRSV antibodies in serum and oral fluids was evaluated in 3 age groups of pigs (4, 8, or 12 weeks of age) inoculated with a type 2 (North American) PRRSV isolate. Serum, buccal swabs, and pen-based oral fluid samples were collected for 63 days following inoculation. Specimens were assayed for PRRSV by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), and for anti-PRRSV antibodies by enzyme-linked immunosorbent assay (ELISA) and indirect fluorescent antibody test (IFAT). Porcine reproductive and respiratory syndrome virus was detected by real-time qRT-PCR in serum for approximately 5 weeks and in oral fluids for approximately 4 weeks postinoculation. Pig age at the time of inoculation had no effect on the quantity or duration of virus in oral fluid samples. Low levels of anti-PRRSV antibody were detected in oral fluid samples by ELISA and IFAT. Although the approach remains to be validated in the field, the results of this experiment suggest that pen-based oral fluid sampling could be an efficient, cost-effective approach to PRRSV surveillance in swine populations.