A pentapeptide with analgesic activity has been isolated from human lung squamous cell carcinoma and from three other types of propagated tumors of human lung small-cell carcinoma (SCC), adenoma (AD) and large-cell carcinoma (LCC) in nude mice. The amino acid sequence of the peptide has been revealed to be H-Thr-Ser-Lys-Tyr-Arg-OH, which is exactly the same as that of neo-kyotorphin, an analgesic peptide originally isolated from bovine brain [(1982) Life Sci. 31, 1733]. No neo-kyotorphin could be isolated from normal lung tissue using the same procedures as those used for carcinomas. The results suggest that the presence of neo-kyotorphin in the lung carcinoma may represent the ectopic expression of peptide hormone. Our findings constitute the first example of a human lung carcinoma producing analgesic peptide.