Porcine reproductive and respiratory syndrome (PRRS) virus exists as two major genotypes, designated as Type 1 (European-like) and Type 2 (North American-like). The role and significance of European-like Type 1 PRRS viruses, recently identified in U.S. swine herds, is poorly understood. It is clear that ignoring Type 1 viruses will lead to additional problems in the control of PRRS. The overall goal of this study was to evaluate the genetic, pathogenic and immunological properties of representative Type 1 isolates from the U.S. and to develop panels of well-characterized serum samples to serve as reference or control materials for diagnostic laboratories and other researchers. Genetic analysis, including the sequencing of whole virus genomes, reveals some important insights into the pathogenesis, diagnosis and evolution of Type 1 PRRS viruses. Funding from this study has provided genomic information for a relatively large number of isolates. The results show that Type 1 viruses are undergoing a remarkable evolution. Type 1 viruses appeared in the U.S. as the result of a limited introduction of viruses, but have shown some remarkable diversification into distinct groups. Our results indicate that this group of PRRS viruses will continue to change genetically. The detection of recombination is especially important, since it indicates that pigs can be infected with multiple isolates. Recombination is a source of new diversity and rapid evolutionary change. Animal challenge studies with four selected European-like Type 1 PRRS virus isolates demonstrated minimal to moderate clinical signs in nursery to grower-age pigs. Pathological lesions in infected pigs euthanized at 14 days post-infection (dpi) were characterized by mild pneumonia with minimal lesions in lymphoid tissue. In animals euthanized at 85 dpi, substantial differences in lesions were noted among treatment groups. Two isolates appeared to cause a broad spectrum of lesions associated with interstitial pneumonia while minimal lesions were associated with the other two isolates. Substantial animal to animal variation within each challenge group existed in antibody responses, duration of viremia and viral loads, as detected by semi-quantitative PCR. Essentially all challenged animals euthanized at 84 dpi still had substantial amounts of PRRS virus present in the tonsils and lymph nodes, indicating the likelihood of persistence for these virus isolates. Robust neutralizing antibody responses were detected following challenge with all four Type 1 isolates. The strongest neutralizing antibody responses were directed against the respective challenge isolates with lower levels of cross-neutralization against other Type 1 PRRS virus isolates and the Type 1 prototype isolate, Lelystad virus. Minimal cross-neutralization with typical North American Type 2 PRRS virus isolates was noted. A major goal of this project was to develop an extensive reference panel of well-characterized pig sera that can be used by diagnostic laboratories as quality control standards for the detection of Type 1 PRRS virus isolates or antibody responses. This panel has been assembled and is linked with full genomic sequence data of the respective challenge isolates, semi-quantitative PCR data, and comprehensive serological data. Samples from this panel will also be used for validation of new diagnostic assays and to ensure that new technologies, such as biosensors, can detect all PRRS virus isolates. These reference panels are already being used in other projects funded by the National Pork Board and others and will provide funding leverage for new proposals submitted to various granting agencies.