Twenty-five renal transplant patients on a triple immunosuppressive regimen of cyclosporine, azathioprine, and prednisone underwent protocol graft biopsies at 1, 2, 3, 6, and 12 months after transplant regardless of renal function. The histological diagnosis was made with the Banff schema. As reported previously, protocol biopsies revealed a high prevalence of subclinical rejection, as well as "borderline" inflammation, despite levels of CsA considered to be in the therapeutic range. Every biopsy was given a score for the severity of the histological changes (the Banff Score for Inflammatory Changes [BSI]), which permitted the generation of a cumulative BSI over the year of follow-up for each patient. At the end of 1 year, normal histology and excellent renal function (mean serum creatinine < 110 mumol/L) were seen only in transplant patients with the lowest cumulative BSI (P < 0.001). These results suggest that repeated inflammation in the renal allograft, even if subclinical, can lead to its dysfunction. Moreover, it would appear that, at least for the present, protocol biopsies may be required to assess adequately the effectiveness of current immunosuppressive therapies in renal transplant patients.