An 8-month-old boy and a 7-month-old girl presented with an acute, Coombs-positive auto-immune haemolytic anaemia and severe hepatitis. The clinical manifestations were pallor, jaundice and hepatomegaly. The liver histology revealed diffuse giant cell transformation and extensive necrosis with central-portal bridging. Combined immunosuppressive regimen with steroids and azathioprine led to prolonged clinical and biological remission with a respective 2 years and 7 months follow up. The girl, however, after 7 months developed a progressive encephalopathy of unknown aetiology, while liver and haematological disease were still under control. She died subsequently from severe recurrent seizures. We conclude that acute Coombs-positive giant cell hepatitis of infancy can be improved by sustained immunosuppressive therapy.