Although both polyomavirus infection and T cell-mediated rejection (TCMR) are characterized by tubulointerstitial inflammation in the renal allograft, these conditions are treated with opposing therapeutic regimens. To gain more insight into the differences between antiviral and alloimmune responses, we performed a case-control study, in which we immunophenotyped the inflammatory infiltrates in renal biopsy specimens with BK polyomavirus-associated nephropathy (BKPyVAN) and specimens with TCMR. Compared with TCMR, BKPyVAN was diagnosed later after transplantation; therefore, BKPyVAN specimens showed more chronic damage than TCMR specimens showed. However, TCMR and BKPyVAN specimens had comparable levels of tubulointerstitial inflammation. Adjustment for confounders in various multivariable models revealed more blood dendritic cell antigen-1(+) (BDCA-1(+)) myeloid dendritic cells (mDCs) present during BKPyVAN (odds ratio, 2.31; 95% confidence interval, 1.03 to 5.16; P=0.04) than during TCMR. Double immunostaining for SV40 and BDCA-1 showed that, during BKPyVAN, BDCA-1(+) mDCs localized in proximity to the polyomavirus-infected tubular epithelial cells. We ensured that time of biopsy after transplantation was not a confounding factor by including additional specimens with late TCMR and protocol biopsy specimens matched for biopsy time. These additional specimens showed amounts of BDCA-1(+) mDCs comparable with amounts in the early TCMR specimens. These results suggest that BDCA-1(+) mDCs, known to be involved in the antiviral immune response during various viral infections, might have a pivotal role during BKPyVAN infection in the grafted kidney.