The impact of cyclosporine A (CsA) therapy in patients with steroid-dependent nephrotic-syndrome (SDNS) on long-term renal function is controversial. Data beyond 5 years are rare. Long-term renal function was evaluated in children with SDNS with and without CsA therapy, especially beyond 5 years. Twenty children were treated with CsA (study group) for a mean of 5.4 +/- 2.2 years (ten patients for 5-11 years). Glomerular filtration rate (GFR) was calculated before and after 3 and 12 months and at latest follow-up of therapy. Fifteen children with cyclophosphamide-treated SDNS without CsA served as controls. In the study group, GFR decreased within 12 months from 136 +/- 19 to 120 +/- 31, to 114 +/- 14 ml/min per 1.73 m(2) at latest follow-up (p < 0.0001). Patients with CsA > 5 years had a GFR of 111 +/- 14 ml/min per 1.73 m(2) at latest follow-up without a GFR below 90 ml/min per 1.73 m(2). No CsA toxicity was found in biopsies. In the control group, GFR dropped within 3 months, from 137 +/- 27 to 130 +/- 24, to 126 +/- 19 ml/min per 1.73 m(2) at latest follow-up (p = 0.1). Patients with and without nephrotoxic CsA therapy showed a drop in GFR. In CsA-treated patients, GFR was about 12% lower at latest follow-up compared with patients without nephrotoxic therapy but always remained within normal range. CsA seems to be safe, even in long-term treatment for more than 5 years.