Porcine reproductive and respiratory syndrome (PRRS) is characterized by late-term abortions and stillbirths in sows and respiratory difficulties in nursery pigs. The disease appeared in Europe and North America at approximately the same time between 1985 and 1990. The PRRS virus was isolated shortly thereafter and demonstrated unexpectedly profound differences between European (Lelystad) and North American (VR2332) isolates as measured by serological crossreactivity and nucleotide sequence similarity. In order to determine the amount of genetic variation in the PRRS virus and to understand the molecular mechanisms of vital evolution, nucleotide sequences of PRRS virus strains were determined. Comparisons among ten U.S. strains showed that variation in primary nucleotide sequence between isolates ranged from 2.5% to 7.9% for ORFs 2-7. In contrast, Lelystad virus was, on average, 35% different from US clones. These results provided direct molecular evidence that US and European PRRSV isolates represented genetically distinct groups of the same viral family. A further analysis of more than 150 isolates in the United States and Canada demonstrated that the PRRS virus in North America represents a single large and diverse genetic group that is distinct from European forms of the virus.