The expression of preprodynorphin has been studied using the Northern blot technique. Ten human cell lines, six small cell lung carcinoma (SCLC), one large cell carcinoma (LCC), two neuroblastoma and one lymphoblast-like cell line, were screened with a preprodynorphin cRNA-probe. Tryptic digestion followed by radioimmunoassay for Leu-enkephalin-Arg6 was used to detect possible translation of the preprodynorphin transcript. Of the ten cell lines investigated we found that all expressed preprodynorphin-mRNA to various degrees, and that this transcript is also translated. Two of the cell lines, neuroblastoma SK-N-MC and SCLC H69, also expressed preproenkephalin-mRNA. This set of cell lines provides a useful model of human origin in which the regulation of the preprodynorphin gene and the posttranslational processing of its products can be studied and compared.