A human betaretrovirus has been characterized in patients with primary biliary cirrhosis (PBC) and the related mouse mammary tumor virus linked with autoimmune biliary disease in the NOD.c3c4 mouse model. Translational studies have been performed in patients who have PBC to investigate the role of viral infection in disease. Patients treated with Combivir experienced significant improvements in hepatic biochemistry, clinical symptoms, and histology with evidence of reversal of ductopenia. Preliminary studies suggest that the NOD.c3c4 mouse model of PBC provides a good model to test safer and more potent drug regimens for future use in trials for patients who have PBC.