Autoimmune hepatitis is a chronic inflammatory disorder of the liver with a fluctuating course, which often requires long-term immunosuppressive therapy in order to prevent fibrosis to the liver. The mainstay of immunosuppressive therapy is the use of corticosteroids, usually in conjunction with azathioprine. However, in a subgroup of patients with severe side effects or intolerance of standard therapy there is a need for alternative immunosuppressive agents. We describe the successful long-term treatment of three patients with severe autoimmune hepatitis with an immunosuppressive regimen consisting of cyclophosphamide and corticosteroids. In the reported patients we were able to induce remission with cyclophosphamide in a dose of 1-1.5 mg/kg bodyweight in combination with a tapering dose of corticosteroids beginning with 1 mg/kg bodyweight. After induction we were able to maintain histology proven remission with low doses of corticosteroids (2.5-10 mg/day) together with 50 mg of cyclophosphamide every other day. With this dose of cyclophosphamide we have neither observed relapse of autoimmune hepatitis nor severe side effects in a cumulative observation period of more than twelve years in the three patients. As a consequence of our favourable experience with cyclophosphamide in the reported cases, we propose cyclophosphamide as an alternative to azathioprine in cases of autoimmune hepatitis with severe side effects of intolerance of standard therapy.