The purpose of this study was to combine our clinical experience with a review of the literature to determine the value of orthotopic liver transplantation in the treatment of both boys and girls with ornithine transcarbamylase deficiency. Three boys younger than 1 year of age with symptomatic ornithine transcarbamylase deficiency (median age, 116 days; range, 40 to 223 days) underwent orthotopic liver transplantation. The patients' growth, developmental progress, ammonia levels, and amino acid levels were analyzed pre- and post-liver transplantation. The clinical courses of the respective patients and the treatment modalities used were compared with published reports from 1978 through 1997. The median follow-up period in these 3 patients was 3.2 years (range, 9 months to 5.2 years). Orthotopic liver transplantation restored normal urea production and stabilized ammonia levels within 24 hours of surgery (median serum ammonia level 24 hours post-liver replacement, 43 micromol/L; range, 30 to 66 micromol/L). After liver replacement, arginine synthesis was normalized; however, plasma citrulline levels remained less than normal in all patients. Linear growth was evaluated in all 3 patients at the time of the most recent follow-up; median z scores for patient height and weight were -2.16 and -1.16, respectively. Standardized intelligence tests showed that 2 of the 3 patients continue to perform at age-appropriate levels. The third child was developmentally delayed pretransplantation at 4 months of age on presentation and continues to perform in a below-average fashion. Orthotopic liver transplantation results in the restoration of normal urea production and serum ammonia levels in the boy suffering from symptomatic ornithine transcarbamylase deficiency. Serum arginine, but not citrulline, levels are normalized, probably because of the persistent intestinal mucosa defect. Patient growth is similar to that in infants undergoing liver transplantation for other causes. When liver transplantation is performed before cognitive impairment occurs, intellectual development is normal, because the risk of additional episodes of hyperammonemia is elevated.