After its discovery in the mid-1990’s postweaning multisystemic wasting syndrome (PMWS) was noted only sporadically in North America for about a decade. However, since late 2004, the porcine circoviral diseases (PCVD) including PMWS have resulted in severe epidemics in various regions throughout North America, and continue to threaten the competitiveness of the North American swine industry. The rise in PCVD in N.A. since 2004 coincides with the isolation of a novel PCV2 strain referred to as PCV2-321 or PCV2b. Based on the near simultaneous emergence of this novel PCV2b and epidemics causing severe morality, some speculate that PCV2b is of enhanced virulence. The objectives of this study were to compare the amount of PCV2 in the tissues and sera of WASTING and HEALTHY pigs from 2 farms infected with PCV2b, and compare to UNAFFECTED pigs originating from a farm with no prior history of PMWS/PCVD. Secondly, PCV2 load in tissues, measured by quantitative PCR, was correlated with the severity of microscopic lesions and PCV2 staining intensity. Ten WASTING and 10 age-matched HEALTHY cohorts from each of two farms, and 10 UNAFFECTED pigs from a PCV2 infected farm with no prior history or diagnosis of PCVD were used in this experiment. From each pig, gross lesions were assessed; sera and multiple tissues were collected. Microscopic lesions suggestive of PCVD, and PCV2 staining intensity were scored (0-3) in all tissues by independent board certified pathologists. Levels of PCV2 DNA (viral load) were measured by quantitative PCV2 PCR (qPCR) in all tissues and sera. The highest viral load was found in WASTING pigs, and across all tissues. By contrast, the lowest PCV2 load was found in UNAFFECTED pigs from the barn with no prior history of PCVD/PMWS. PCV2 load in UNAFFECTED pigs was significantly lower than in HEALTHY pigs from farms suffering PCVD. Thus, in farms affected with PCVD/PMWS “WASTING” and visually “HEALTHY” pigs may be appropriately termed “clinical”, “pre-clinical”, whereas healthy pigs in UNAFFECTED farms may be appropriately termed “sub-clinical”. Viral load, as measured by qPCR, was strongly correlated with PCV2 staining intensity and microscopic lesions characteristic of PCVD. Although the diagnosis of PCVD in individual animals requires microscopic examination and PCV2-specific staining of multiple tissues, qPCR is suited for population based monitoring of live animals, for example, the monitoring of control or vaccination programs. Sera, gluteal (ham) muscle, or inguinal lymph node are all appropriate diagnostic samples to submit for the monitoring of PMWS/PCVD in commercial nursery and finisher pigs. Finally, the results of this project indicate that the biological relevance of PCV2 genotypes (2a, 2b) needs to be further clarified. The simultaneous presence of both PCV2a and 2b in UNAFFECTED pigs from a farm with no history of PMWS/PCVD implies that PCV2b is of no greater virulence than PCV2a. Although PCV2 DNA sequencing is of great academic interest, its value for commercial farms is less obvious.