An immunohistochemical study with two rabbit polyclonal antibodies I-AR76 and CA-08-351 against Endothelin-1 (ET-1) was performed in 133 human thyroid specimens: 5 normal thyroids, 30 multinodular goiters (15 toxic and 15 nontoxic), 20 Graves' diseases, 5 Hashimoto's thyroiditis, 26 adenomas (6 Hürthle cell, 16 toxic and 4 nontoxic), 30 classic papillary carcinomas, 3 minimally invasive follicular carcinomas, 1 widely invasive follicular carcinoma, 3 undifferentiated carcinomas and 10 medullary carcinoma. All normal thyroids, non toxic multinodular goiters and non toxic adenomas, 4 (66%) Hürthle cell adenomas, 3 (15%) Graves' diseases, 1 (33%) case of minimally invasive follicular carcinoma showed rare follicular cells with weak cytoplasmic immunoreactivity. Many immunoreactive follicular cells, with or without oxyphilic changes, were observed in all specimens of Hashimoto's disease, while the lymphocytic infiltrate was always negative. Twenty-seven (90%) classic papillary carcinomas were positive. Immunoreactivity was intracytoplasmic, weak in 14 cases and intense in 13. The cells of toxic adenoma and toxic multinodular goiter were negative, whereas the acellular stroma was intensely positive in both cases. Medullary and undifferentiated carcinomas were negative. These results show ET-1 immunoreactivity in normal and pathological human thyroids. In particular, the high content of this peptide in the thyroid papillary carcinoma suggests that ET-1, whose mitogenic role has recently been emphasized, could be involved in the growth of this tumor.