Reactivation of BK polyomavirus (BKV) is increasingly recognized as a cause of failure of renal allografts. Since no specific treatment is available for this infection, early diagnosis is important, as it allows for early intervention and possible recovery of renal function. Forty-four consecutive renal transplant biopsies performed over a 2-year period were included in the study. In addition to evaluation of renal biopsy tissue sections using routine histochemical stains, CD3, CD20, BK virus immunostains using the specific BK virus and the SV40 antibodies and electron microscopy studies were performed. None of the transplant cases but one exhibited classical histologic viral changes. Viral particles were seen by EM in 19%, and BK-virus positivity was identified in only 43% of these cases. CD20-rich inflammatory infiltrates predominated in cases in which either positive BK stain and/or viral particles were identified ultrastructurally. A combined approach using electron microscopic and immunohistochemical evaluation can be utilized effectively to identify BK virus-associated nephropathy at an early phase facilitating early clinical intervention.