The goals of this project was: 1) to determine the feasibility of using an innovative porcine alveolar macrophage cell line, designated ZMAC-1, for the production of a PRRS modified live virus (MLV) vaccine and 2) to compare the efficacy of vaccine virus grown in this alternate host to that propagated in the only other cell line known at the initiation of this study to support the growth of PRRS virus, namely the simian cell line MA-104 and its derivative the MARC-145 line. Initially, the ZMAC-1 cells were found to be readily susceptible to the MLV vaccine Prime Pac PRRS (Schering-Plough Animal Health). Moreover, after the third passage of the virus in ZMAC-1 cells, a yield comparable to that achieved when using MARC-145 cells was obtained. To evaluate the vaccine potential of both ZMAC-1 cell-grown virus, a standard immunization-challenge study was conducted. In this case, six 8 week-old pigs were injected with an equivalent dose of the Prime Pac vaccine grown in either ZMAC-1 or MARC-145 cells while two additional groups of three animals were not immunized. Four weeks later, all vaccinated and one of the PRRS virus-naïve groups were challenged with an “atypical PRRS abortion storm” virus isolate (NADC-20). One outcome of the study was that the Prime Pac MLV vaccine grown in either cell line was equally effective at preventing the body weight loss of PRRS virus-naïve pigs that had been exposed to the heterologous virus 7 days earlier. However, the vaccine virus grown in ZMAC-1 cells was significantly more effective than the MARC-145 derived one at reducing the extent of viremia and also at eliminating virulent virus from the lungs at 7 and 10 days post-challenge, respectively. The observation that the type of cell line used to grow the PRRS MLV vaccine can improve the level of protective immunity elicited by the same vaccine virus against a genetically divergent virulent PRRS virus has important implications for the prospect of developing a highly effective vaccine against this pathogen. Namely, the results of this study suggest that the effectiveness of a PRRS MLV virus vaccine is not, as it is commonly believed, only determined by its genetic similarity to the challenge virus, but is also influenced by how it is produced. The results of this study provide great hope that an effective MLV vaccine against PRRS virus can be developed.