The objectives in the studies described herein were to evaluate the use of an antemortem in vitro test as an indicator in identifying commercial breeding stock lines with high and low susceptibility to PRRSV and to evaluate the pigs from lines selected from the first objective in an experimental infection model. Macrophages have been shown to be the cell type PRRSV preferentially infects and subsequently manipulates to achieve efficient replication and production of progeny virions. The in vitro assay was therefore designed to evaluate the percentage of macrophages derived from peripheral blood monocytes that are susceptible to infection in culture by PRRSV. In order to address objective one, six genetically diverse lines of pigs maintained as commercial breeding seed-stock were evaluated for differences in their in vitro susceptibility to PRRSV. The specific aim of objective one was to determine if the in vitro PRRSV flow cytometric assay could be utilized to detect the existence of genetic variability in the susceptibility of the host to PRRSV infection. From the results of the six screened lines, two genetically distinct lines with opposing in vitro results were selected for further study to confirm the results of the antemortem in vitro assay screening;The second objective was to infect pigs from lines demonstrated to have high and low susceptibility in the in vitro assay in order to evaluate variation of disease traits in vivo. The average percentage of PRRSV-infected macrophages in culture was shown to differ statistically between the two chosen lines, indicating that the susceptibility of macrophages in culture varied. To investigate these differences in vivo, PRRSV challenge studies were conducted in four independent replicates. Pigs were experimentally infected and evaluated for disease susceptibility using the flow cytometric assay, clinical presentation of respiratory disease, macroscopic lesions, microscopic lesions, and virus titers. The overall aim of the investigations reported here were to provide evidence for a genetic basis to susceptibility to PRRSV-induced infection and disease utilizing both an in vitro PRRSV susceptibility assay and experimental challenge and to evaluate the usefulness of the in vitro flow cytometric assay in predicting susceptibility upon challenge.