BK virus infection can be associated with interstitial inflammation, tubulitis without viral cytopathic effect, and negative in situ hybridization for viral DNA. We evaluated the consequences of increased immunosuppression in 32 viruric patients, with such acute cellular rejection-like changes in allograft biopsies (n = 50). When follow-up information was available, complete creatinine response, decrease in urine viral load (VL), and improvement in overall Banff grade for acute rejection were only seen in 13 (27%) of 49, 7 (21%) of 33, and 10 (39%) of 26 episodes of graft dysfunction, respectively. Histologic response was not always accompanied by clinical response. This low rate of response to antirejection therapy suggests that interstitial nephritis in a subset of these patients was secondary to viral infection. The presence of high VL (>1.0 E+05 copies/mL) was associated with low immune cell function values (129 +/- 99 ng of adenosine triphosphate per milliliter, P = .08) and with significant development of viremia after antirejection treatment (5/9 [56%] versus 0/24 [0%] in patients with low VL, P < .001).