The distribution of immunoreactive transforming growth factor-alpha (TGF-alpha) was studied in non-neoplastic human major and minor salivary glands using an immunoperoxidase assay in conjunction with an antiserum to human TGF-alpha. The ductal cell components of all major and minor salivary glands were found to contain significant amounts of TGF-alpha immunoreactivity. In contrast, acinar and myoepithelial cells consistently lacked immune reaction product in both types of glands. Occasionally, an asynchronous pattern of TGF-alpha ductal cell immunoreactivity was observed in specific ducts within a section. Also, intraductal secretions, when present, were found to contain TGF-alpha immunoreactive material. Ductal cells and connective tissue from salivary glands samples showing significant lymphocytic infiltration and loss of acinar cells exhibited higher levels of TGF-alpha immunoreactivity than normal salivary gland samples. These observations demonstrate, for the first time, the presence of TGF-alpha immunoreactivity in specific structural components of non-neoplastic human major and minor salivary glands. It will be important in future studies to determine whether alterations in TGF-alpha expression are detectable in diverse types of salivary gland tumors.