Understanding of the molecular basis of virulence and attenuation of porcine reproductive and respiratory syndrome virus (PRRSV) is important for the development of a safe and efficacious vaccine. Prime Pac (PP) is an attenuated vaccine strain of PRRSV which is being used in our laboratories as a source of gene(s) for the generation of chimeric constructs in the background of a highly virulent PRRSV derived from an infectious clone (FL12) to examine the molecular determinants of virulence and attenuation. To facilitate these studies, we generated a full-length cDNA clone of the PP vaccine strain by serially replacing the genomic fragments of the FL12 with the corresponding regions from the PP strain. The virus rescued from this newly assembled cDNA clone (PP18) exhibited in vitro growth properties and in vivo apathogenic characteristics of the parental PP virus. Using pregnant sows as the experimental model of reproductive pathogenesis, we have been able to unequivocally demonstrate the clearly contrasting phenotypes of the virulent and the attenuated viruses derived from the infectious clones (FL12 and PP18). The development of an infectious clone derived from a bona fide attenuated PRRSV vaccine strain should significantly facilitate ongoing studies to determine the molecular basis of virulence and attenuation.