Biliary glycoprotein (BGP), a member of the carcinoembryonic antigen gene family, is a cell surface glycoprotein that has both a transmembrane domain and a cytoplasmic domain. BGPs consist of at least four isoforms (BGPa, b, c, and d) and function in vitro as Ca(2+)-dependent homotypic intercellular adhesion molecules. The mRNA expression of BGP gene was investigated in specimens of primary and metastatic cancer tissues from 15 patients with primary lung cancer (six squamous cell carcinomas, five adenocarcinomas, and four small cell carcinomas). The specimens were also compared with normal adjacent tissues of the same individuals with squamous cell carcinoma. BGP mRNA expression was increased in carcinomatous tissues of the primary site, especially in squamous cell carcinoma, but was not detected in adjacent normal tissues by Northern blot analysis or in situ hybridization. Interestingly, BGP mRNA expression was apparently decreased in metastatic lesions compared with the primary site in the six individuals with squamous cell carcinoma. Furthermore, a loss of BGPa isoform was observed by reverse transcriptase-polymerase chain reaction in four of six patients with squamous cell carcinoma. These results suggest that the reduction of BGP expression may play an important role in the process of metastasis through decreasing adhesive interactions with surrounding cells, especially in squamous cell carcinoma.