Somatic mutations in the genes for G-protein-coupled receptors which regulate intracellular levels of cyclic AMP have been found in several regions coding for the receptors of melanocyte-stimulating hormone, adrenaline, luteinizing hormone, rhodopsin and thyrotropin. The mutations found in the thyroid-stimulating hormone (TSH) receptor are restricted to cells of hyperfunctioning thyroid adenomas and other thyroid tumors. They are thought to lead to a constitutive activation of the receptor independent of TSH. We have developed a temperature-gradient gel electrophoresis (TGGE) assay starting with the amplification of a part of exon 10 of the TSH-receptor gene to screen tissue of thyroid tumours. TGGE allows the detection of point mutations even if there are only a few cells with somatic mutations in tissue sections.