Clinical evidence suggests the possible influence of estrogen on the biologic behavior of thyroid neoplasm. In this study we evaluated the distribution and characteristics of intracellular receptors for estrogen in normal and neoplastic thyroid tissue obtained from 54 patients. Forty-two percent of all specimens assayed by the protamine sulfate precipitation technique had a detectable intracellular binding site for estrogen. Differentiated carcinomas (eight of eight) and adenomas (seven of nine) had high incidences of receptors compared with goiter (five of 23) and normal thyroid (three of eight). However, there were no detectable receptors for estrogen in medullary carcinomas of the thyroid (0 of six). Also, carcinomas and adenomas had higher receptor contents than did goiter and normal differentiated thyroid tissue. There was no significant difference in the affinity of estrogen for receptors among the different histologic groups. There were both 4S and 8S receptor types, which were specific for estrogen. The binding of estrogen to thyroid tissue and differentiated neoplasm originating from thyroid tissue were comparable to the binding of estrogen to other hormone-dependent normal and neoplastic tissues.