Atrial natriuretic factor (ANF) N-terminal (ANF 1–98) and C-terminal (ANF 99–126) fragments were determined by radioimmunoassay in human plasma. Mean basal plasma ANF N-terminal concentrations in 9 healthy subjects were 461 ± 58 fmol/ml,significantly (p<0.0001) higher than ANF C-terminal concentrations ( 4.8 ± 0.5 fmol/ml). Central volume stimulation by one hour head-out water immersion (WI) induced a significant (p<0.01) increase of the C-terminal peptide levels to 11.6 ± 2.3 fmol/ml,paralleled by a significant (p<0.001) increase of the N-terminal fragment levels to 749 ± 96 fmol/ml. Increases of plasma concentrations of both fragments upon WI correlated significantly (r=0.71;p<0.05). These data suggest cosecretion of the N-terminal fragment with the C-terminal fragment of pro ANF 1–126 following a physiological stimulus of ANF release in man.