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To determine the role of epidermal growth factor (EGF) receptors in thyroid tumorigenesis, EGF binding was compared in membranes from malignant and from benign thyroid tumors. Surgical specimens were obtained from 28 patients with thyroid carcinomas (3 papillary, 13 follicular, 6 undifferentiated, and 6 medullary carcinomas) and from 30 patients with benign thyroid tumors (15 scintigraphically functional and 15 nonfunctional nodules). In 30 cases normal tissue adjacent to the tumor was also obtained. EGF binding was seen to be increased not only in thyroid carcinomas but also in benign thyroid tumors, particularly in functional thyroid adenomas. The highest EGF binding was found in undifferentiated carcinomas. A direct comparison of the EGF binding characteristics in tumor and adjacent normal thyroid tissue revealed that the increased binding of EGF is due mainly to an increase in the number of binding sites rather than an alteration in receptor affinities. EGF binding capacities were 18.4±16.7 fmol/mg protein in thyroid carcinomas and 10.5±5.2 fmol/mg in the corresponding normal tissue ( P<0.05, K 0.84±0.26 nM, n=11). In autonomously functioning thyroid adenomas binding capacities were 14.2±8.2 fmol/mg in the nodules and 8.9±4.8 fmol/mg in normal tissue ( P < 0.01, K 0.73±0.62 nM, n = 15). In conclusion, EGF receptor levels are increased not only in malignant thyroid tumors but also in well-differentiated benign thyroid nodules. The data indicate that an increased expression of EGF receptors, although likely to be important in the regulation of thyroid growth in vivo, is not by itself associated with malignant cell transformation and loss of differentiated function. [ABSTRACT FROM AUTHOR]