Objective: To determine the clinical and epidemiological features of infants with extreme hyperbilirubinemia who require exchange transfusion (ET). Study design: Term and near-term infants admitted to a paediatric hospital over a 5-year period in La Paz, Bolivia, were included in the study if they met the following criteria: age less than 30 days; total serum bilirubin (TSB) levels ≥428 μmol/L (≥25 mg/dL) on admission and if they had undergone an ET. Results: Fifty-six infants were identified during the study period. Most of them were exclusively breastfed (98.2%). Median age at admission was 7 days. Weight loss of more than 12% since birth, as well as dehydration, was registered in more than one-third of cases. Extreme hyperbilirubinemia was considered as secondary to increased enterohepatic circulation (EHC) in most cases (73%). The mean TSB level on admission was 531.8 μmol/L (31.1 mg/dL). Fifteen infants (26.8%) showed signs of acute bilirubin encephalopathy (ABE). Early ABE was reversible after ET in most cases but all infants with advanced ABE developed severe kernicteric sequelae. Nine patients (16.1%) developed adverse events attributable to ET. Conclusions: Dehydration and weight loss in breastfed infants appeared to be an important factor associated with extreme hyperbilirubinemia and secondary brain damage during the first week of life. This may well be avoided if signs of ABE and its associated conditions are identified appropriately by follow-up programmes. © 2008 The Children's Hospital Dr Ovidio Aliaga U.