To achieve specific and efficient expression of transfected suicide gene in malignant mesothelioma cells, we explored the 5-flanking region (2.2 kb) of the calretinin gene as a tumor-specific promoter. RT-PCR analysis demonstrated the expression of calretinin mRNA in two human malignant mesothelioma cell lines (H2052 and 211 H). A reporting vector containing the calretinin promoter (pCAL-LUC) exhibited relatively high luciferase activity in these cell lines. After transfecting an expression vector containing the calretinin promoter-bound thymidine kinase gene (pCAL-TK) into the cells, we examined their sensitivity to ganciclovir (GCV). In the mesothelioma cell lines, the pCAL-TK transfected cells became about 100 times more sensitive to GCV than the parental cells. The calretinin promoter seems to be a promising candidate as a specific and efficient promoter in malignant mesothelioma.