mRNA isolated from medullary carcinoma of the thyroid (MTC) in six patients with the inherited multiple endocrine neoplasia syndrome type 2 and cervical metastases in two patients with sporadic MTC was screened for the presence of calcitonin and proopiomelanocortin (POMC) related sequences by blot hybridization analysis. All tumors were found to contain mRNA hybridizing to a calcitonin-specific probe. However, POMC-related sequences were detected only in RNA preparations purified from the metastases of MTC. Compared with the POMC mRNA occurring in the human pituitary gland, the size of the RNA species hybridizing to the POMC-specific probe was larger in the metastases of both of the patients investigated. cDNA complementary to mRNA from one of the metastases was cloned into pBR 322. From this library two plasmids were isolated containing inserts which were completely homologous to a sequence of 190 nucleotides from the 3'-end of human pituitary POMC mRNA. In conclusion, 1) hybridization and nucleotide sequence analyses demonstrate that the POMC gene is expressed in MTC metastases; 2) the observed length difference between MTC and pituitary mRNAs suggests differences in expression or processing; 3) no expression of the POMC gene was found in six primary tumors.