Porcine circovirus type 2 (PCV2) associated diseases (PCVAD) have been an important cause of mortality and economic loss to the swine industry. The importance of virulence between different virus genotypes known as PCV2a and PCV2b is poorly characterized. The purpose of this study was to compare in vitro, differences in the virus replication rate and induction of lymphocyte death due to apoptosis caused PCV2a and PCV2b in vitro. Previous work in our laboratory demonstrated that stimulated lymphocytes had increased PCV2 viral replication and apoptosis compared to non-stimulated cells. This study investigated the differences in these parameters in cells infected with either PCV2a or PCV2b. We found that infection with PCV2b, reported to be more virulent, resulted in increased replication and apoptosis early following infection of cells at 24 hours post infection (HPI), independent of stimulation, compared to PCV2a. Depending on the mitogens used, the increased viral replication of the PCV2b isolate varied compared to the PCV2a virus. However, by 120 HPI, the replication rate of the PCV2a isolate was greater than the rate of the PCV2b in all cases. These results suggest that the PCV2b virus replicates quickly in stimulated lymphocytes which may make control by the pig’s immune system less effective in controlling PCV2b virus levels compared to PCV2a. An increased level of cell death or apoptosis of lymphocytes infected with PCV2b was observed at 72 HPI in PCV2b cells stimulated with concanavalin A (ConA), while pokeweed mitogen (PWM) increased PCV2b apoptosis at 120 HPI. PCV2b may have been due to a reduced number of susceptible cells due to In addition, we demonstrated that there was an increased rate of cell death in CD8+ cytotoxic T lymphocytes compared to the other populations. These findings are significant as this is the population of cells that recognizes and destroys virally infected cells and may be a mechanism by which the virus for persists in the pig. Reduced viral replication observed at the later time periods may have been due to fewer cells due to apoptosis. The differences in rate of viral replication and cell death in infected lymphoid cells may provide a potential explanation for the increased disease associated with PCV2b infection compared the level of disease observed with PCV2a. The findings of this study suggest that the type of stimulation to which the lymphoid cells are exposed as well as the genotype of the virus may be important in determining the disease severity by individual animal. Further work needs to be performed to confirm these results in vivo.