Summary. We here report a patient who developed a high titer antibody to factor VIII (FVIII) during gram-negative urosepsis caused by enterobacter cloacae after complete resection of rectal cancer. The patient initially presented with a life threatening spontaneous hematothorax and multiple large haematomas. Coagulation studies revealed a severe FVIII deficiency <1% with a high FVIII antibody titer of 64 BU. The bleeding responded rapidly to infusions of recombinant factor VIIa. After achievement of a partial remission (FVIII activity 28%) by combined immunosuppressive therapy (prednisone, cyclophosphamide, plasmapheresis and immunoadsorption), subsequently, two relapses occurred following steroid tapering. Resumption of prednisone and cyclophosphamide treatment combined with immunoadsorption induced a second and third remission, respectively. After resection of a papillary carcinoma of the bladder 6 months later and continuous immunosuppressive therapy with cyclophosphamide, FVIII levels remained stable within normal ranges. This clinical course suggests that the cause of inhibitor formation against FVIII resulting in severe acquired haemophilia was multifactorial and was initiated by the gram-negative urosepsis and probably by the underlying malignancies.