BACKGROUND BK virus (BKV) infection of kidney transplant patients is an increasing problem and is thought to be secondary to potent immunosuppressive therapy. BKV infection progresses to BKV nephritis (BKVN) in approximately 8% of transplants and in half of these cases the graft is lost. METHODS We used an interferon-gamma enzyme-linked immunosorbent spot (ELISPOT) assay to measure the cellular immune response to peptides encoding BKV large T antigen. Eight kidney transplant patients with BKVN were tested at the time of diagnosis of BKVN and then after resolution of active BKV infection. RESULTS When total spot counts from all peptide pools were combined, the mean ELISPOT signal per 10,000 cells at the time of BKVN diagnosis was 23.1 (range 3.4-59.7), with a median of 21.8. This increased to 70.2 (range 5.4-189.4) with a median of 37.0 (P=0.1216) after resolution of active BKV infection. To further increase specificity of response, we counted the number of peptide pools with ELISPOT activity of greater than 10 spots per well after subtraction of background. The mean number of pools fitting this criteria at the time of BKVN diagnosis was 2.1 (range 0-8) with a median of 1.5; this increased to 8 (range 1-18) and a median of 6.5 after recovery (P=0.0338). CONCLUSIONS This demonstrates that recovery of cellular immune response to large T antigen corresponds with resolution of active BKV infection. This may prove useful in monitoring patients' cellular immunity and recovery from active BKV infection when treated with reduction in immunosuppressive therapy.