Human polyoma virus infection was diagnosed by a needle biopsy of the allograft in two kidney transplant recipients. Viral infection was initially suggested by the occurrence of markedly enlarged tubular epithelial cells with nuclear atypia and chromatin basophilia. Confirmatory evidence was obtained by immunohistochemistry in both cases, and electron microscopy in one instance. Case 1 presented as a refractory interstitial nephritis and underwent allograft nephrectomy. Case 2 showed viral infection concurrent with acute cellular rejection. The rejection initially responded to treatment, but recurred twice on subsequent followup. A review of the literature indicates that asymptomatic infection, ureteric stricture and hemorrhagic cystitis are other possible manifestations of polyoma virus in the human urogenital tract.