The rat calcitonin gene has recently been shown to encode a novel peptide (rat calcitonin gene-related peptide, rCGRP) thought to be produced in nervous tissue after tissue-specific RNA processing. This peptide has so far been identified only in rat tissue, by immunocytochemistry and immunoassay. We now report the isolation of a related (89% homology) peptide from human tissue (hCGRP) which we have sequenced using a novel mass spectrometric approach, fast atom bombardment (FAB) mapping. The human peptide differs significantly from the predicted rCGRP structure in four positions in the amino acid sequence (three effecting charge changes), and the presence of a disulphide bridge and an amide, surmised in the rat work, is proven in the hCGRP molecule. hCGRP was present in plasma from 10 patients with medullary thyroid carcinoma (MTC) and in 6 MTC tumours removed at surgery, suggesting the tissue distribution may differ from that in the rat where the peptide is reported to be absent from thyroid tissue. hCGRP is shown to have biological activity and it is possible that its presence in MTC plasma may be responsible for some of the symptoms in this disease.