Cystic fibrosis transmembrane conductance regulator (CFTR) has been considered to be involved in the regulatory pathway of biliary mucin secretion. We investigated expression of CFTR protein and mRNA in 24 livers with hepatolithiasis, in 6 with cholangiocarcinoma, and in 12 histologically normal livers. According to the histologic features of chronic proliferative cholangitis, hepatolithiasis was subdivided into inflammatory cell infiltration predominant (N = 14) and fibrosis predominant (N = 10). The mean signal density of CFTR in overall hepatolithiasis and in histologically normal livers was 1.23 +/- 0.15 and 1.01 +/- 0.13, respectively (P > 0.05). The CFTR protein (1.60 +/- 0.18) and mRNA (1.09 +/- 0.15) in inflammatory cell infiltration predominant patients were significantly higher (CFTR protein, 1.01 +/- 0.13; mRNA, 0.75 +/- 0.11) than in control subjects (P < 0.05), whereas those in fibrosis-predominant patients (CFTR protein, 0.72 +/- 0.15; mRNA, 0.55 +/- 0.13) were less than in control subjects (P < 0.05). CFTR protein (1.27 +/- 0.17) in patients with cholangiocarcinoma was not different from that of control subjects (1.01 +/- 0.13). CFTR expression in hepatolithiasis patients was rather heterogeneous but was closely related to the histology of bile ducts.