This study examined the effect of porcine reproductive and respiratory virus (PRRSV) on how genes are expressed in porcine alveolar macrophages (PAMs). PAMs were chosen for this study because they are the primary targets of infection by PRRSV. Serial analysis of gene expression (SAGE) was used here because it allowed us to look at most of the genes expressed in these cells. We determined the normal levels that genes are expressed in normal, non-infected PAMs and then compared this to the gene expression levels in PRRSV-infected PAMs at several time points after infection. It is well established that many pathogens cause changes in expression of specific genes that act to protect the host and clear the infection. This type of response was not seen in these cells. There was surprisingly little in the way of a protective response. Of particular interest was the minimal expression of genes that are involved in attracting other immune cells to the area of the infection. Additionally, there was no response by genes that cause inflammation. This is the first comprehensive study to show the actual breadth of inhibition of an immune response in PAMs by PRRSV. However, the results have also given us tantalizing clues to the mechanism(s) behind this inhibition. There are specific cellular proteins that control the expression of the protective genes and future studies will look at how the virus may be inhibiting their function. This may possibly lead to a means for a producer to intervene that may act to limit or end an active PRRSV infection by restoring the animal’s natural protective mechanisms.