Transforming growth factor-alpha (TGF-alpha) is frequently coexpressed with its receptor, epidermal growth factor receptor (EGF-R), in several types of carcinoma and sarcoma. It is believed that this results in an autocrine stimulation of tumor growth in these tumors. We have found that TGF-alpha and EGF-R/c-erbB RNAs were co-expressed at significantly higher levels in papillary thyroid carcinomas and their lymph-node metastases than in non-neoplastic thyroid tissues. We also observed a low level of expression of RNA specific for insulin-like growth factor I in these tumors, which was highest in a lymph-node metastasis. Autocrine stimulation by TGF-alpha may thus be a common feature of papillary carcinomas of the thyroid. Since EGF is known to induce proliferation and dedifferentiation of normal thyroid cells in culture, TGF-alpha and its receptor may play an important role in thyroid carcinogenesis.