Primary biliary cirrhosis (PBC) is one of the few nonalcohol-induced liver pathologies that causes false positives in assays of carbohydrate-deficient transferrin (CDT) for diagnosing alcohol abuse. CDT was quantified by isoelectric focusing-immunoblotting-laser densitometry (IEF-IB-LD) analysis of serum from 117 women: 57 PBC patients, 20 alcohol abusers, and 40 healthy donors. Only 5% (3 of 57) of PBC patients were positive at the densitometric cutoff value chosen (> 90% specificity). Serum samples from 15 PBC patients were further evaluated by IEF-IB-LD and CDTect chromatography-RIA. Receiver-operating characteristic (ROC) analysis showed that IEF-IB-LD better discriminated between PBC and alcohol abuse than CDTect did. By ROC analysis, mitochondrial autoantibodies to pyruvate dehydrogenase antigen M2 detected by enzyme immunoassay yielded optimal test performance for diagnosing PBC. Of six patients falsely positive for CDT by CDTect, five (83%) tested M2-positive. Thus, abnormal CDT results should be further evaluated by mitochondrial antibody testing in patients with findings compatible with PBC.