We studied the characteristics of epidermal growth factor (EGF) receptors in plasma membrane fractions derived from normal and diseased human thyroid tissues. The mean maximal specific binding of EGF to membrane fractions of normal thyroid tissue (n = 25) was 1.46 +/- 0.47 (+/- SD) fmol/mg protein. The maximal specific binding was higher than the upper limit of the normal range (2.40) in 12 of the 39 (31%) differentiated carcinomas, 2 of the 3 (67%) undifferentiated carcinomas, and 1 squamous cell thyroid carcinoma. In contrast, the maximal specific binding in samples derived from adenomas (1.13 +/- 0.91), adenomatous goiters (0.92 +/- 0.56), and hyperplastic (Graves') thyroids (1.57 +/- 0.61) was not different from that in normal thyroid tissue. Scatchard plot analysis revealed that all thyroid membrane fractions had two classes of specific receptors for EGF. The mean association constant for the high affinity EGF receptors in normal thyroid tissue was 7.9 +/- 2.9 (+/- SD) X 10(9) mol/L-1, and the capacity was 22.9 +/- 7.0 fmol/mg protein. The capacity of the high affinity receptors was higher (P less than 0.05) in differentiated carcinoma (37.2 +/- 25.5) and undifferentiated carcinoma (32.7 +/- 11.6) than in normal thyroid tissue. In one squamous cell carcinoma, the capacities for the two classes of binding sites were about 15-fold greater than in normal thyroid tissue. In contrast, the association constants of the high affinity receptors from carcinomas (differentiated, 6.9 +/- 2.8; undifferentiated, 11.8 +/- 4.1; squamous cell, 8.2) were similar to that of normal thyroid tissue. In the thyroid tissues from eight patients with Graves' disease the capacity of the high affinity binding sites (37.5 +/- 12.3 fmol/mg protein) was higher than that in normal tissue, but the affinity (4.4 +/- 1.6 X 10(9) mol/L-1) was less, and the maximal specific binding was similar in the two types of tissue. These results suggest that a significant increase in the number of high affinity EGF receptors may play a role in the pathogenesis of human thyroid carcinoma.