Atrial cardiocytes contain granules typical of protein-secreting cells, and atrial extracts are known to contain a powerful natriuretic and diuretic activity and to possess smooth muscle relaxant activity. A variety of active atrial peptides have been isolated, including a family of related peptides showing natriuretic, diuretic and smooth muscle relaxant activities in rat and human atria; these peptides were named atrial natriuretic factor (ANF). Another unrelated peptide from pig atria, cardiodilatin, is thought to possess only smooth muscle relaxant activity. Its partial amino acid sequence shows no homology with ANF sequences. The sequence analysis of a large form (106 amino acids) of ANF and of ANF complementary DNA clones indicates that cardiodilatin and ANF peptides are synthesized from a common precursor. This precursor also contains a signal peptide sequence expected of a secretory protein. We now describe the complete structure and sequence of the human gene for this novel hormone precursor that we call pronatriodilatin.