Investigations during the last few years supported the existence of two major forms of cardiac peptides. In the heart, a prohormone of 126 amino acid residues (CDD-1-126) is stored, while CDD-99-126/ANP (= αANP) is the circulating form in the blood plasma. By use of a similar isolation procedure, as used for the isolation of circulating CDD-99-126/ANP, a biological active peptide, strongly related to CDD-99126/ANP, was purified from urine, indicating excretion from the kidneys. Sequence analysis shows that the main form of urinary cardiodilatin is a 32 amino acid residue containing molecule (urodilatin-95-126) similar to CDD-99-126/ANP except N-terminal extension by four amino acid residues. The prolongation first of all indicates that urodilatin is not derived from a plasma form and obtained by filtration and renal clearance. Secondly, it demonstrates that urodilatin undergoes a different posttranslational process during excretion than CDD-99-126/ANP. Both, synthetic human cardiodilatin (CDD-99-126)/atrial natriuretic peptide (ANP) and urodilatin (95–126) are phosphorylated by the catalytic subunit of cAMP-dependent protein kinase at a serine residue in position 104. Phosphorylated peptides exhibit decreased relaxing potency compared to unphosphorylated peptides. CDD-99-126/ANP is rapidly removed from the circulation by clearance and proteolytic degradation. Inactivation of CDD-99-126/ANP in the kidneys occurs by an endoprotease-24.11 present in the cortical membranes. Due to the enzymatic reaction a major cleavage occurs within the ring structure between Cys105 and Phe106. In contrast, N-terminal extension by four amino acid residues (Thr-Ala-Pro-Arg) and cAMP-dependent phosphorylation of CDD-99-126/ANP inhibit proteolysis by kidney cortical membranes.