Objective: To determine the renal side effects of long-term, low-dose cyclosporine therapy (initial dose, 5 mg/kg body weight per day) in patients with autoimmune idiopathic uveitis. Design: Cohort study with at least 2 years of follow-up. Setting: A teaching hospital in Paris, France (Hospital Pitie-Salpetriere). Patients: Sixteen patients with idiopathic autoimmune uveitis who were normotensive and had normal renal function before treatment. Cyclosporine was administered orally for at least 2 years at an initial dosage of 5 mg/kg body weight per day. Results: After 2 years of treatment, the serum creatinine level increased by 35 +/- 5 mumol/L (0.40 +/- 0.06 mg/dL) (95% Cl, 25 to 46 mumol/L, [73 +/- 4 to 108 +/- 4 mumol/L]). Creatinine clearance decreased significantly from 120 +/- 5 mL/min to 75 +/- 4 mL/min. Glomerular filtration rate decreased from 116 +/- 8 mL/min to 75 +/- 3 mL/min, and effective renal plasma flow decreased from 455 +/- 24 mL/min to 338 +/- 30 mL/min (P < 0.05). Cyclosporine induced a significant increase in serum uric acid, total cholesterol, and serum potassium levels. Blood pressure was normal in all patients before treatment; 81% (95% Cl, 64% to 98%) of these patients developed hypertension after 24 months of treatment. Blood pressure was controlled with a single drug in all but two patients. Conclusions: In patients with healthy native kidneys, long-term cyclosporine therapy, even at a low dose (5 mg/kg per day), is nephrotoxic and is associated with a high incidence of hypertension.