Detection of apoptotic cells and of immunoreactivity to transforming growth factor alpha (TGF-alpha) and to its ligand, epidermal growth factor receptor (EGFR), was studied in 20 cases of parathyroid adenoma. The DNA nick-end labelling method revealed that 85% of these adenomas contained apoptotic cells. Detection rates of TGF-alpha and EGFR were very high, but neither TGF-alpha nor EGFR was correlated to apoptosis. As TGF-alpha exerts its effect via EGFR, the concomitant demonstration of the two factors occurring in both the adenomatous tissue and the surrounding rim of normal tissue may reflect a significant mutual association. The markers were located mainly within the cytoplasm, indicating their important role in growth regulation, cell differentiation and cell function. The synchronous expression of TGF-alpha and EGFR in both parathyroid adenomas and normal glandular parenchyma suggests that these functions may be mediated by an autocrine mechanism.