Polyadenylated RNA, extracted from a human medullary thyroid carcinoma, was translated in cell-free systems prepared from wheat germ and reticulocyte lysates. The major product of the translations was a protein of 15,000 MR which was immunoprecipitated specifically with an antiserum to synthetic human calcitonin. Addition to the translation reactions of microsomal membranes, prepared from canine pancreas, resulted in the partial disappearance of the 15,000 MR polypeptide and the concomitant appearance of a smaller peptide (11,000 MR), also immunoprecipitated specifically by antisera to calcitonin. These results indicate that human calcitonin is synthesized in the form of a precursor of 15,000 MR and suggest that the precursor contains a leader sequence that is cleaved from the polypeptide by enzymes associated with microsomal membranes. © 1979.