Semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR) was used to study the T-cell receptor (TCR) beta-chain variable (Vbeta) region gene families expressed by T cells in 28 patients with primary biliary cirrhosis (PBC), 20 normal controls, and 9 patients with other chronic inflammatory hepatic diseases. We hypothesized that activation and clonal proliferation of T cells would lead to biases in the T-cell repertoire of patients with PBC. Freshly harvested T cells from both peripheral blood and liver tissue were examined for evidence of biased Vbeta utilization. Individuals varied considerably in their pattern of Vbeta expression, but several significant differences were noted in the PBC group. In peripheral blood, the mean level of Vbeta6.1,3 expression was greater in PBC patients than in normal controls. In the liver of PBC patients, the mean level of Vbeta6.1,3 expression was even higher than in the peripheral blood, indicating intrahepatic accumulation of these T cells. The mean level of Vbeta6.1,3 expression was not significantly different in the blood compared with liver in patients with other liver diseases. Expression of Vbeta7 and Vbeta13.1 was also significantly greater in the liver than in the blood of PBC patients, but similar trends were also seen in the control liver group. These data show that specific alterations in the TCR repertoire are present in the blood and liver of patients with PBC.