Up to 60% reduction of renal function has been reported after orthotopic liver transplantation (OLT) in patients receiving cyclosporine. We prospectively investigated renal function and histopathology in 16 children on triple immunosuppression therapy during 3 years after OLT. Cyclosporine was administered in 3 doses/day to preschool children. The median age at OLT was 5.4 years. Determinations of chromium 51-labeled ethylenediaminetetraacetic acid, p = aminohippuric acid, lithium, and sodium clearances, measurements of serum and urinary electrolytes, and urinary concentration tests were performed. Renal biopsy specimens were taken 18 and 36 months after transplantation. The mean glomerular filtration rate was 121.5 ml/min per 1.73 m2 before transplantation, 86.3 at discharge, and 119.4 36 months after OLT. Hyperuricemia, hyperkalemia, and reduced urinary concentrating capacity were common. Hyperkalemia occurred in 13% to 19% of the patients, only during the first 6 months. Hyperuricemia and reduced concentrating capacity occurred with incidences of 17% to 44% and 40% to 63%, respectively. Histopathologic changes were mild, and severe nephrotoxic effects of cyclosporine was not seen. However, tubular atrophy, mesangial matrix increase, and mesangial cell proliferation were common. We conclude that triple immunosuppression with cyclosporine administration, in three doses per day, to small children and careful renal follow-up ensure good renal function after OLT.