Simultaneous measurements of plasma atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (GMP) concentrations were performed in children with various forms of cardiac diseases (n = 22) and in control children (n = 29). In healthy children, plasma ANP and cyclic GMP levels ranged between 2.4 and 98.0 (mean 45.8) pg/mL and 0.2 to 2.8 (mean 1.40) pmol/mL, respectively. In children with cardiac diseases, plasma ANP (26.0 to 499.7 [mean 188.7] pg/mL) and cyclic GMP (0.2 to 6.0 [mean 2.9] pmol/mL) levels were significantly higher than in control children (both P less than .0001). There was a linear correlation between the two values in children with cardiac diseases (P less than .01). Because the effects of ANP to target tissues are mediated by cyclic GMP, cyclic GMP appears to be a marker for the cellular responses to ANP. The increased cyclic GMP levels in children with cardiac diseases indicate that ANP exerts its effects on target organs also in states of chronically enhanced ANP levels.