Increase of liver enzymes during therapy with endothelin receptor antagonist (ERA) because of pulmonary arterial hypertension (PAH) has been observed quite frequently the cause of which is unknown. Here we describe a female patient who suffered from autoimmune hepatitis (AIH) type I [positive for antinuclear (ANA) and antiactin antibodies] who developed systemic sclerosis (SSc) with PAH. AIH was treated with corticosteroids and azathioprine, and PAH with the ERA sitaxentan. Reactivation of AIH was observed in the course of therapy with sitaxentan as shown by an increase of liver enzymes, immunoglobulin G globulins, the reappearance of antinuclear and antiactin antibodies and the induction of a further AIH marker antibody reacting with the soluble liver/liver pancreas antigen. Therapy with ERA for pulmonary hypertension may increase the risk for development or exacerbation of AIH.