Objective: To report on an infrequent association of pathologies causing considerable increase in bilirubin production and a signifiant decrease in its excretion. Description: The third pregnancy of an RhD negative woman. Her first child was normal and delivered to term and did not receive Rhogam. The second pregnancy was problematic due to Rh isoimmunization. She delivered a child to term, who required three exchange transfusions, but died on the 8th day of life. The third child was delivered at term, ORh positive, direct Coombs positive and had stump bilirubin of 6.5 mg/dl and hematocrit at 44%. Five hours after birth the child was jaundiced. Phenobarbital and intensive phototherapy were introduced. Hyperbilirubinemia was soon controlled, but relapsed whenever phototherapy was discontinued. On the 10th day of life the child received a transfusion for significant anemia. As jaundice persisted to the 13th day, associated Gilbert syndrome was considered and DNA sequence analysis was requested. The test demonstrated a mutant homozygote genotype UDPT1A1[TA] 7TAA. Phototherapy remained necessary until the 17th day of life and she was discharged from hospital the following day, after bilirubinemia had been controlled. She returned for follow-up and exhibited normal growth and neurological development. Comments: This case demonstrates the significance of increased bilirubin production/decreased bilirubin excretion causing intense hyperbilirubinemias and, in the abnsence of vigorous treatment, kernicterus. The effectiveness of intense phototherapy has also been demonstrated, reducing the risks of more aggressive treatments such as exchange transfusion. It also provides evidence of the importance of bilirubinemia follow-up until complete resolution. Copyright © 2005 by Sociedade Brasileira de Pediatria.815421424Gilbert, A., Lereboullet, P., La cholemie simple familiale (1901) Semaine Medicine, 21, pp. 241-243Bosma, P.J., Chowdhury, J.R., Bakker, C., Gantla, S., De Boer, A., Oostra, B.A., The genetic basis of the reduced expression of bilirubin UDP-Glucuronosiltransferase 1 in Gilbert's syndrome (1995) N Engl J Med, 333, pp. 1171-1175Bancroft, J.D., Kreamer, B., Gourley, G.R., Gilbert syndrome accelerates development of neonatal jaundice (1998) J Pediatr, 132, pp. 656-660Roy-Chowdhury, N., Deocharan, B., Bejjanki, H.R., Gantla, S., Roy-Chowdhury, J., Koliopoulos, C., The presence of a Gilbert-type promoter abnormality increases the level of neonatal hyperbilirubinemia (1997) Hepatology, 26, pp. 370ABosma, P.J., Inherited disorders of bilirubin metabolism (2003) J Hepatol, 38, pp. 107-117Kaplan, M., Hammerman, C., Rubaltelli, F.F., Vilei, M.T., Levy-Lahad, E., Renbaum, P., Hemolysis and bilirubin conjugation in association with UDP-glucuronosyltransferase 1A1 promoter polymorphism (2002) Hepatology, 35, pp. 905-911Kaplan, M., Renbaum, Levy-Lahad, E., Hammerman, C., Lahad, A., Beutler, E., Gilbert syndrome and glucose 6 phosphate dehydrogenase deficiency: A dose-dependent genetic interaction crucial to neonatal hyperbilirubinemia (1997) Proc Nat Acad Sci USA, 94, pp. 12128-12132Sampietro, M., Lupica, L., Perrero, L., Comino, A., Di Montemuros, F.M., Capellini, M.D., The expression of uridine diphosphate glucuronosyltransferase gene is a major determinant of bilirubin level in heterozygous beta-thalassemia and in glucose-6-phosphate dehydrogenase deficiency (1997) Br J Haematol, 99, pp. 437-439Galanello, R., Piras, S., Barella, S., Leoni, G.B., Cipollina, L., Perseu, L., A cholelitiasis and Gilbert's syndrome in homozygous β-thalassemia (2001) Br J Haematol, 115, pp. 926-928Valaes, T.N., Harvey-Wilkes, K., Pharmacologic approaches to the prevention and treatment of neonatal hyperbilirubinemia (1990) Clin Perinatol, 17, pp. 245-273Facchini, F.P., Bianchi, M.O., Brasileiro Silva, B.A., Fototerapia no tratamento de caso grave de doença hemolítica do recémnascido (2000) J Pediatr (Rio J), 76, pp. 387-390Jackson, J.C., Adverse events associated with exchange transfusion in healthy and ill newborns (1997) Pediatrics, , http//www.pediatr.org/cgi/content/full/99/5/e7, [serial on line] May [cited 2001 Feb 21];99(5)Roy-Chowdhury, J., Roy-Chowdhury, N., Unveiling the mysteries of inherited disorders of bilirubin glucuronidation (1993) Gastroenterology, 105, pp. 288-293Laforgia, N., Faienza, M.F., Rinaldi, A., D'Amato, G., Rinaldi, G., Iolascon, A., Neonatal hyperbilirubinemia and Gilbert's syndrome (2002) J Perinat Med, 30, pp. 166-169Watchco, J.F., Daood, M.J., Biniwale, M., Understanding neonatal hyperbilirubinemia in the era of genomics (2002) Semin Neonatol, 7, pp. 143-152