Hyponatremia in patients with small cell lung cancer can be caused by tumor production of arginine vasopressin (AVP) and result in the syndrome of inappropriate antidiuretic hormone. In evaluating the expression of AVP mRNA from tumor and tumor cell line specimens from five patients with small cell lung cancer and hyponatremia (presumed to have the syndrome of inappropriate antidiuretic hormone), we found that the tumors and tumor cell lines from two of these five patients expressed AVP mRNA. The RNA samples from the three patients with undetectable AVP mRNA expressed abundant atrial natriuretic factor (ANF) mRNA. Analysis of specimens from three patients with small cell lung cancer and normal serum sodium levels revealed no detectable AVP mRNA expression, and samples from only one of these three patients' specimens expressed detectable ANF mRNA. The AVP and ANF peptide levels in lysate preparations of the tumor cell lines from four of these patients were tested by radioimmunoassay and confirmed the gene expression data. These studies demonstrate ectopic production of ANF mRNA in small cell lung cancer specimens from patients with this cancer and the syndrome of inappropriate antidiuretic hormone. These findings will be of particular interest if future studies demonstrate that ectopic ANF production can cause sodium abnormalities in patients with small cell lung cancer.