The aim of this preliminary, prospective, longitudinal study was to evaluate the effects on graft function and viral loads of modulation of immunosuppressive therapy based upon serial noninvasive monitoring of urine and serum viral loads with real-time polymerase chain reaction among unselected renal transplant recipients. Thirty-nine renal transplant recipients with follow-up times of 7.8 +/- 4.3 months were monitored monthly with urine and serum samples to measure BK viral load. Interventions such as gradual reductions of mycophenolate mofetil and/or tacrolimus were performed when repeated urine and serum viral loads were >10(5) and >10(3) copies/mL, respectively. Among 271 samples, the patients were divided into 6 groups: negative urine (group = 1; n = 10) and negative serum (group 2; n = 25) versus BK viral loads that were intermittent (urine: group 3; n = 24 and serum: group 4; n = 11) versus persistent (urine: group 5; n = 5 and serum: group 6; n = 3). In groups 3-4 we observed the higher viral loads in the urine than in the serum (10(3): 21; 10(4): 1; 10(5): 1; 10(6): 1 vs 10(2): 8; 10(3): 2; 10(4): 1). The timing of resolution of viremia was more rapid than viruria. In groups 5-6 we observed the greatest viral load and greater number in urine. The overall incidences of viruria and viremia were 74.3% and 35.9%, respectively. The overall rates of clearance of viruria were 26/29 recipients (89%) and viremia, 11/14 recipients (78%). Only 10 patients (25.6%) needed extensive reduction of immunosuppression. No modifications of serum creatinine levels and no rejection episodes were observed. In conclusion this preliminary analysis suggested that serial, noninvasive monitoring of viral load allows gradual premptive reduction of immunosuppression with consequent strong reduction in viral load.