To investigate whether cyclosporin (CsA) causes chronic renal damage 38 renal allograft biopsies were performed 1 to 4 years after transplantation in 28 CsA-treated patients, in the absence of rejection or acute CsA nephrotoxicity. Blind, semi-quantitative light microscopic examination showed that interstitial fibrosis plus tubular atrophy occurred more often in CsA-treated patients than in patients treated with azathioprine. The degree of interstitial fibrosis correlated with high cumulative CsA dose during the first 6 months of treatment, as well as with the number of acute CsA nephrotoxic episodes, which suggests that the findings are an effect of chronic CsA nephrotoxicity. Maintenance doses of CsA (2.3-10.7 mg/kg/day) seemed to contribute little to the renal damage. The pathogenesis of the observed lesions is not known. A high trough CsA level at the time of biopsy correlated with the degree of interstitial mononuclear cell infiltrate in the renal tissue. The results thus demonstrate chronic morphological changes in renal allografts from CsA-treated patients. Avoiding high CsA doses may be a way of preventing this side-effect. Until this has been confirmed, the risk of chronic renal damage must be taken into consideration when new clinical trials of CsA are being planned.