This study was designed to determine whether four peptide hormones consisting of amino acids 1-30-long-acting natriuretic hormone (LANH), 31-67 (vessel dilator), 79-98 (kaliuretic hormone), and 99-126 (atrial natriuretic hormone [ANH])-of the 126 amino acid atrial natriuretic prohormone increase the circulating concentration of testosterone in healthy humans (n = 30). Vessel dilator, kaliuretic hormone, LANH, and ANH increased the circulating concentration of testosterone 3.8, 2.6, 3.9, and 3.4-fold, respectively (p < 0.01 for each), when infused at 100 ng/(kg of body wt . min) for 60 min. The increases in testosterone lasted 2.5-3 h after cessation of the respective atrial natriuretic peptides' infusions. ANH, vessel dilator, LANH, and kaliuretic hormone increased luteinizing hormone (LH) 3-to 8.4-fold (p < 0.001) during infusion, with the maximal increase in LH being 6.7- to 11.7-fold (p < 0.001) secondary to these cardiac hormones. Vessel dilator and kaliuretic hormone increased LH before increasing testosterone in a sequential fashion. These data suggest that four peptide hormones-ANH, LANH, vessel dilator, and kaliuretic hormone-increase the circulating con-centrations of LH and testosterone in humans.