Nodular regenerative hyperplasia (NRH) of the liver is a local hyperplastic response of hepatocytes, probably due to vascular abnormalities. Since it was shown in a few case reports that NRH may be associated with antiphospholipid antibodies (APA) we wanted to analyze the relevance of APA in patients with this disease. Sera from 13 patients with histologically defined NRH were tested for APA by an in-house ELISA using as antigens cardiolipin (CL), beta2-glycoprotein I (beta2-gp I), phosphatidylserine (PS), and thromboplastin (TP), a mixture of different phospholipids and phospholipid-binding proteins. As controls, sera from patients with serologically and histologically defined autoimmune liver diseases (primary biliary cirrhosis n = 14; autoimmune hepatitis n = 14) without histological evidence for NRH as well as from 14 healthy blood donors were analyzed. 77% of the NRH patients had APA. In 46% they were directed against CL. In contrast, only 14% of the patients with autoimmune liver diseases and 14% of the healthy controls had anti-CL antibodies (p < 0,05). Antibodies to beta2-gp I and TP did not discriminate between NRH and autoimmune liver diseases. Anti-PS antibodies were not observed. These data indicate that determination of anti-CL antibodies in NRH may help to identify a subgroup of patients in whom an 'organ-specific antiphosholipid syndrome' of the liver may be involved in the pathogenesis.