Immune tolerance (IT) in hemophilia A patients with anti-factor VIII antibodies is generally based on daily factor VIII administrations. Here we report the preliminary results of an immune tolerance regimen based on recombinant high-dose (400 U/kg) factor VIII boluses administered at 48-hour intervals. Two high responder hemophilia A patients aged 2 and 3 years received this treatment without the need of permanent venous access. In both cases the IT regimen caused an anamnestic response of less than three weeks' duration and an antibody reduction to less than 5 Bethesda units was achieved in about 8-10 weeks. In the child with a more prolonged follow-up the inhibitor became undetectable after four months and factor VIII recovery at 6 months was > 85%. This intermittent high-dose regimen seems to be effective in rapidly inducing immune tolerance and seems particularly suitable for very young children in whom it may be useful to avoid the risks and to reduce the psychological burden of permanent venous access.