Thyrotropin binding characteristics and adenylate cyclase (AC) activity of thyroid plasma membranes were studied in 52 tissues from normal and diseased human thyroids. Data from normal glands, Graves' goiters, non toxic multinodular goiters and nodular and perinodular tissue of toxic nodular goiters show the same basal, TSH- and NaF- stimulated adenylate cyclase activities (no. = 45; 34.1 +/- 3.2 (m +/- SE), 378 +/- 43, 298 +/- 48 pmol cAMP x min-1 x mg membrane protein-1), the same stimulability of AC by TSH (11.3 +/- 1.4--fold over basal level) and by NaF (8.1 +/- 1.8-fold), the same apparent TSH binding equilibrium constants (5.6 +/- 0.7 and 406 +/- 57 nM) and the same TSH binding site concentrations (2.2 +/- 0.4, 27.8 +/- 5.9 pmol x mg membrane protein-1). Alterations of the TSH receptor and of the AC were detected in membranes from tumoral and metastatic lymph node tissues from thyroid papillary carcinoma and in the thyroid tissue from post-radioiodide therapy thyroiditis. These observations suggest that: (i) hyperthyroidism in Graves' disease or toxic nodular goiter does not result in and is not a consequence of an alteration in the TSH receptor-adenylate cyclase system; (ii) there is no evidence supporting a relationship between the studied membrane properties and clinical or histological status; (iii) membrane abnormalities detected in thyroid carcinoma vary widely; (iv) studies of these membrane alterations might be of interest in the therapeutic management of thyroid carcinoma and may lead to a better understanding of the receptor-adenylate system.