Cyclosporin A (CyA) has recently been shown to be effective in frequently relapsing, steroid-resistant or steroid-dependent childhood nephrotic syndrome (NS). Wider acceptance has been hindered by considerations of cost, toxicity and drug-dependent maintenance of remission. Black children in Africa with NS are mainly steroid-unresponsive and alternative therapies therefore need to be assessed. We report on 8 of 11 children who completed at least 24 weeks of CyA therapy; 6 (2 with membranous nephropathy (MEM) and 4 with focal glomerulosclerosis) showed no improvement, while 2, both with MEM, achieved remission while on CyA therapy and remained in remission for 1 and 3.5 years, respectively, after cessation of therapy. This may have been the natural course of the disease. Of the children who were unresponsive to CyA, 3 died in renal failure 8-30 months after cessation of CyA therapy, 1 had a rising creatinine value when last seen, and 2 were lost to follow-up. CyA trough levels varied between 180 and 875 ng/ml and peak levels between 563 and 1,950 ng/ml. Of 5 repeat renal biopsies, 3 were performed at the end of 24 weeks of treatment and revealed no evidence of CyA toxicity. Two biopsies revealed chronic CyA toxicity. CyA should therefore be used with caution at lower dosages and monitored at currently accepted lower trough levels in children with NS in Africa.