The effects of human leukocyte interferon on BK papovavirus (BKV) infection in 41 recipients of renal transplants were studied as part of a randomized, double-blind, placebo-controlled trial. Eight transplant recipients demonstrated fourfold or greater rises in antibody to BKV, and three excreted BKV in urine. Neither seroconversion nor excretion was reduced by interferon administration. No clinical syndromes could be clearly linked to BKV infection. BKV was also relatively resistant to the in vitro effects of interferon. Pretreatment of interferon-sensitive human fibroblasts with up to 620 units of interferon/ml resulted in a loss of viral infectivity of one log or less. Continuous exposure of infected cultures to these interferon levels reduced BKV titers by 1.5-2.9 logs, whereas continuous exposure to lower concentrations of interferon had less effects. The levels shown to be marginally effective in vitro were considerably higher than those achieved in these patients' sera.