At therapeutic drug levels, the functional changes which occur are a reduction of glomerular filtration rate and renal plasma flow. At higher doses, morphological changes develop which may result, particularly in severe cases, in acute or chronic renal failure. The threshold for the development of irreversible vascular-interstitial lesions mainly depends on the increment of serum creatinine, age and drug dosage or drug blood level. Based on the experience with cyclosporin A (CyA), the following recommendations have been made for its clinical use, especially in patients with autoimmune diseases. The initial dose should not exceed 5 mg/kg body weight and the dose should be reduced if blood CyA levels are over 250 ng/ml; in addition, a dose reduction is recommended if serum creatinine values exceed 30% of pre-treatment values or if other signs of CyA toxicity, such as hepatotoxicity or hypertension, are found. Strict adherence to these suggestions should allow treatment of patients for prolonged periods without irreversible morphological lesions.