In contrast to its importance in improving renal graft survival, nephrotoxicity is the most serious side effect of cyclosporine. Dosage reductions of CsA mitigate its nephrotoxic effect. However, CsA nephrotoxicity is still a problem in clinical transplantation. In this study the relationships among preexistent chronic histological lesions, donor age, and renal function after transplantation in 100 CsA treated renal allograft patients are described. Multivariate data analysis revealed a significant statistical effect of the presence of preexistent chronic histological lesions on nonimmediate function (-.42, less than 0.0001) that was relatively twice as large as the effects of cold ischemia time (-.21, less than 0.05). Also in predicting creatinine clearance at 1 and 3 months, preexisting chronic histological lesions had the most important effect (-.39, less than 0.0001; -.57, less than 0.0001, respectively), whereas the presence or absence of rejection episodes was less predictive (.24, less than 0.001; .20, less than 0.01, respectively). Preexistent chronic histological lesions had also significant effects in predicting conversion to azathioprine and prednisolone, because of CsA nephrotoxicity (-.42; less than 0.0001). The degree of CsA nephrotoxicity therefore varies according to the presence of preexistent chronic histological lesions. Because of the increase of these lesions with age, one has to be aware of an exaggerated CsA toxicity, especially in the older donor age group and in older patients treated with CsA for various reasons.