Although much research has been performed on porcine reproductive and respiratory syndrome virus (PRRSV), little quantitative information is available on the relationships between virulence and in vivo virus replication, among isolates recovered at different times in the history of PRRS, or the relative levels of virulence associated with individual virus isolates. In this study, the in vivo growth properties of virulent field isolates and attenuated PRRSV isolates were compared. The results show that virulent PRRSV isolates exhibit longer and more elevated levels of viremia, induce faster and more intense humoral immune responses, negatively affect body weight gain, induce higher death rates, and cause more severe clinical signs in a respiratory disease model. We found that the more virulent field isolates grew to significantly higher levels in pigs than did cell-culture adapted isolates. We concluded that the pathogenic consequences and immunological responses of pigs to PRRSV are directly related to viral load in acute infection as reflected in viral titers in blood.