We describe the case of a teenager who developed fever, arthritis, cutaneous vasculitis and severe pancytopenia 3 weeks after the third vaccination boost with a recombinant hepatitis B vaccine. Bone marrow examination showed paucity of late myeloid elements and, subsequently, maturation arrest. Interferon-gamma (IFN-gamma) production by peripheral blood mononuclear cells from the patient was dramatically increased. An underlying immune predisposition (HLA-DR3) may have indirectly enabled the vaccine to trigger a hepatitis B virus-specific cytotoxic T-lymphocyte response. It is therefore possible that the pancytopenia was induced by a dysregulation of the CD8+ T-cell compartment via increased IFN-gamma production.