OBJECTIVE: Primary biliary cirrhosis (PBC) is an autoimmune disease affecting small intrahepatic bile ducts of the liver, causing destruction of the epithelium that results in eventual fibrosis and scarring. We still lack a complete epidemiological description of this disease, although interesting geographic differences in prevalence have been described. One consistent feature has been the relative scarcity of men with PBC. In fact, published ratios of women to men range from 3:1 to as high as 22:1. Thus far, the only clinical difference reported between men and women with PBC is a putative higher risk of hepatocarcinoma in men. Previous serological studies have shown that about 95% of all patients possess antimitochondrial antibodies to members of the highly conserved 2-oxo-acid dehydrogenase family of proteins, namely pyruvate dehydrogenase complex E2 (PDC-E2), branched-chain 2-oxo-acid dehydrogenase complex E2 (BCOADC-E2), and 2-oxo glutarate dehydrogenase complex E2 (OGDC-E2). However, there has been no information as to whether there is a difference in serological response between men and women. Using the serological hallmark of antimitochondrial antibodies (AMAs) and taking advantage of the availability of recombinant mitochondrial autoantigens, investigations were performed to determine if there were any serological differences between men and women with PBC. METHODS: Sera were collected from 88 patients with PBC, of whom 46 were men and 42 were women. Using a combination of immunoblotting and enzyme-linked immunoabsorbent assay (ELISA) against beef heart mitochondria (BHM), recombinant PDC-E2, BCOADC-E2, and OGDCE2, we determined the relative autoantibody reactivities of our study population. RESULTS: Both men and women with PBC produced high titer antimitochondrial antibodies. The frequency of reactivity was similar in both groups and included, in descending order, PDC-E2, E3BP (Protein X), BCOADC- E2, and finally OGDC-E2. More importantly, antigenic specificity was nearly identical regardless of gender. CONCLUSIONS: AMAs are the serological hallmark of PBC in both men and women, and there is no significant difference in reactivity between the two groups of patients.