Porcine reproductive and respiratory syndrome (PRRS) remains one of the most important diseases of swine since first recognition in 1987. It emerged simultaneously in Europe and the United States, and has spread worldwide. The causative agent, a virus (PRRSV), was discovered in Lelystad, Netherlands in 1991. While significant progress has been made in understanding the biology of the virus, effective control measures remain elusive. Of particular concern is the state of the currently available vaccines. The live attenuated vaccines provide protective immunity against homologous challenge, but not against heterologous viruses. Furthermore, outbreaks of PRRS in the field have been associated with vaccine virus. Therefore, production of rationally designed vaccines requires a better understanding of virus-host interactions and host immunity. It is broadly accepted that PRRSV subverts the host innate immune response, resulting in insufficient protection and viral persistence. In this study, we sought a better understanding of this phenomenon. Both the sensitivity of PRRSV to exogenous swine interferon beta (IFNβ), and the induction of IFNβ were examined. It was found that in MARC-145 cells, sensitivity to IFNβ was variable, when cells were treated with IFNβ for at least 4 hours prior to infection. Interestingly, resistant strains in MARC-145 cells were found to be sensitive in alveolar macrophages (PAMs). Surprisingly, a sensitive strain in MARC-145 cells was observed to be resistant in PAMs. To test IFNβ induction, three field strains, 2 parental infectious-clone derived, and 8 chimeric viruses were examined. It was demonstrated that IFNβ was produced following PRRSV infection in a strain and time dependant manner. Two effector proteins of the type I IFN pathway (ISGs), Mx1 and TNFα, were examined. It was observed that Mx1 production correlates with IFNβ induction. Interestingly, TNFα was not induced, in an apparent target-specific inhibition. Finally, a discussion is presented based on the genetic components of the chimeric viruses and their ability to induce IFNβ. The findings in this study are compared to the findings in other studies. It is proposed that modulation of IFNβ responses result from multigenic effects of the virus.