Technical Abstract: In a previous series of studies focused on the diagnosis of porcine reproductive and respiratory syndrome (PRRS), we tested sera, alveolar macrophages and various tissues for their suitability as diagnostic samples when collected from acutely and persistently infected pigs. The results of these studies indicated that the causative virus (PRRS virus, PRRSV) could usually be isolated from any of several kinds of samples (serum, tonsils, lungs, and alveolar macrophages) during acute infection, but from only alveolar macrophages during later stages of infection. However, during a recent experiment that was initially unrelated to our investigations of PRRS, we found that alveolar macrophages may sometimes be the diagnostic sample of choice even during acute infection. Details of this fortuitous observation are presented.