A defect in saliva secretion is observed in human diseases such as Sjogren's disease. It is also observed during radiation therapy of cancer of head and neck when the parotid glands get incidentally irradiated. Therefore, the understanding of the mechanisms of regulation of the synthesis and secretion of salivary gland proteins is important. However, the direct investigation of molecular mechanisms that regulate the synthesis and secretion of salivary gland proteins has been hindered by the fact that longterm cultures of acinar cells have not been available. Also, the regulatory mechanisms of growth, differentiation, and transformation of acinar cells cannot be investigated until such cultures are established. Recent advances in tissue culture technology utilizing different approaches have made it possible to establish long-term cultures of epithelial cells including acinar cells from normal rat and human salivary glands, and human pleomorphic adenoma and adenocarcinoma. These approaches include: (i) immortalization of salivary gland cells by inserting T antigen genes from SV40 or polyoma viruses into the genome of these cells; (ii) maintenance and growth of epithelial cells from human pleomorphic adenoma and adenocarcinoma on a special substrate; (iii) maintenance and growth of acinar cells from normal adult salivary gland in specific serum free growth media; and (iv) maintenance of cells from parotid glands of transgenic animals that are programmed to develop salivary gland tumors. The purpose of this review is to critically analyze the potential usefulness and limitations of immortalized cell lines which have been generated by insertion of exogenous genes and compare them with those which have been produced by other methods.