The tumoral production of brain natriuretic peptide (BNP) was studied using 9 small cell lung cancer (SCLC) cell lines which were established from patients with small cell lung cancer. BNP cDNA fragment was generated from 20 microg total RNA which was prepared from the human right cardiac atrium by reverse transcription-based polymerase chain reaction. Expression of BNP mRNA was detected in 30 microg total cellular RNA from these cell lines by RNase protection assays in 5 of 9 SCLC cell lines. Radioimmunoassays using 125I-radiolabeled human BNP(1-32) and antihuman BNP(1-32) antibody detected immunoreactivity in cell pellets from SCLC cell lines which had detectable BNP mRNA. BNP immunoreactivity in the cell pellets corresponds with the data from BNP mRNA analyses. We conclude that SCLC cells have detectable BNP mRNA by RNase protection assay and BNP immunoreactivity in the cells.