The present investigation was designed to determine whether atrial natriuretic peptides consisting of amino acids 1-30 [i.e. pro-ANF-(1-30)], 31-67 [i.e. pro-ANF(31-67)], 79-98 [i.e. pro-ANF-(79-98)], and 99-126 [i.e. atrial natriuretic factor (ANF)] of 126-amino acid ANF prohormone have a negative feedback on their own and each others' release. Thirty healthy human subjects were studied with infusion of 100 ng/kg BW.min for 60 min of each of the respective peptides. Pro-ANF-(1-30) decreased the circulating concentrations of pro-ANF-(31-67) and ANF 51% and 89%, respectively. Pro-ANF-(31-67) decreased the circulating concentration of ANF by 55% and the peptides immunologically recognized by the pro-ANF-(1-30) RIA by 58% [this assay recognizes pro-ANF-(1-30) (50%) and pro-ANF-(1-98) (50%)]. Pro-ANF-(79-98) decreased the circulating concentration of ANF by 40%, pro-ANF-(31-67) by 31%, and the peptides recognized by the pro-ANF-(1-30) RIA by 46%. ANF decreased the circulating concentration of pro-ANF-(31-67) by 40% and the peptides recognized by pro-ANF-(1-30) RIA by 38%. Infusion of pro-ANF-(1-30), -(31-67), -(79-98), and -(99-126) also decreased the excretion of the other atrial natriuretic peptides measured in the urine by 32-84%. Infusion of vehicle only did not result in any decrease in these atrial natriuretic peptides in either plasma or urine. These data taken together indicate that each of the respective atrial natriuretic peptides inhibits the release, rather than breakdown, of each other, as increased breakdown would have resulted in their urinary concentrations being increased. This study further indicates that because pro-ANF-(1-98) was decreased in the circulation secondary to pro-ANF-(31-67) and pro-ANF-(79-98) infusions, they inhibit their own release, as they are both derived from pro-ANF-(1-98).