Cyclosporin A (CsA) was introduced in recent years for the treatment of lupus nephritis in patients with steroid resistance or in those with severe corticosteroid toxicity. Our previous study on paediatric patients showed that Neoral (a new microemulsion formulation) had better bioavailability than CsA capsules. To evaluate the clinical efficacy of Neoral in children with lupus nephritis compared with conventional therapy, we performed an open randomized study on 40 children, ranging from 9 to 14 yr old, with class III-V lupus nephritis and heavy proteinuria. They were randomly assigned to either Neoral (5 mg/kg/day), administered q.12.h, or prednisolone (2 mg/kg/day) plus cyclophosphamide (2 mg/kg/day) for 1 yr. Both groups showed a significant decrease in proteinuria (Neoral: 4.62 +/- 1.93 to 0.35 +/- 0.29 g/day, P < 0.05; prednisolone plus cyclophosphamide: 4.52 +/- 1.86 to 0.62 +/- 0.21 g/day, P < 0.01). The CH50 haemolytic assay titre decreased after 1 yr of Neoral treatment (26.5 +/- 0.9 to 21.4 +/- 2.2 U/ml, P < 0.05). Serum C3 and anti-double-stranded (ds) DNA antibody levels also fell with Neoral (C3: 86.2 +/- 6.8 to 76.3 +/- 4.5 mg/dl; anti-ds DNA antibodies: 14.1 +/- 3.2 to 8.2 +/- 1.4 IU/ml, P < 0.05). The Neoral group had a significant increase in growth rate over the prednisolone plus cyclophosphamide group (8.2 +/- 1.1 cm/yr vs 2.7 +/- 0.6 cm/yr, P < 0.01) with improvement of growth status. During the study period, patients tolerated Neoral well with no significant changes in renal function, liver function or lipid profile. Our study implies that Neoral appears to be effective in suppressing proteinuria. Neoral should be regarded as being adjunctive therapy, perhaps with a steroid-sparing effect, in paediatric lupus nephritis. However, its long-term use awaits further studies.