Liver transplantation in children less than one year of age has been shown to provide results comparable to those achieved in adults. The results of liver transplantation in the very young child (newborn up to three months of age) have not previously been examined, most likely because of the very small number of transplants performed (average 7.8 transplants/year in US 1988-1995, UNOS statistics). The results of liver transplantation in this extremely young age group from three large pediatric liver transplant centers have been combined and analyzed. A total of 22 children (representing 35% of US patients by UNOS statistics) were transplanted before the age of three months. Median followup is 1.5 years. Mean age at the time of transplant was 57 + 30 days, and patient weight at the time of transplant was 3.8 + 1.0 kg. Etiology of liver disease included: neonatal hepatitis (46%), hemochromatosis (18%), and other (36%). Cadaveric grafts were utilized in 85% of patients (60% reduced size grafts, and 25% full size grafts), and living donor reduced size grafts were utilized in 15%. ABO identical grafts were used in 65% of patients, and ABO compatible grafts in 35%. ABO incompatible grafts were not used. Induction therapy with antilymphocyte preparations was used in 36% of patients (OKT3- 6, ATGAM-2). Maintenance immunosuppression was cyclosporin-based in 86% and tacrolimus-based in 14%. Acute rejection was observed in 45% of patients, and 20% of those experiencing rejection required OKT3 for rejection reversal. Median time to first rejection episode was 13 days (mean + SD, 30 + 42 days). Actuarial patient and graft survival at 1, 2, and 3 years were: 60% /55%; 60% /46%; and 60% /46%. These patient survival rates are slightly lower than previously published from each institution in children less than 1 year of age (p=ns). Retransplantation was performed in 14% at a median time to retransplant of 1.56 years (mean + SD, 1.19 + 0.68 years). Hepatic artery thrombosis and portal vein thrombosis each occurred in one patient (5%). Both died before retransplantation. Two of three patients requiring retransplantation had chronic rejection. Conclusions: 1) liver transplantation provides acceptable patient and graft survival rates in children less than three months of age, although success rates may be lower than that of children less than one year of age, and 2) rejection in children less than 3 months of age occurs with a frequency and severity similar to that of older children, and 3) The incidence of vascular thrombosis is similar to other pediatric age groups.