The integrative and sustained effects of small increments in atrial natriuretic factor (ANF) on hemodynamic, renal, and hormonal function are still unclear. Accordingly, we have studied the sequential effects of 24-h, low-dose infusion (2.4 pmol.kg-1.min-1) of rat Ile-ANF or vehicle alone (control) in six normal sheep receiving a constant sodium intake. Compared with control observations, ANF infusions induced a threefold rise in venous plasma ANF and a sustained twofold rise in plasma guanosine 3',5'-cyclic monophosphate. Systolic arterial and right atrial pressures fell promptly and remained significantly reduced for the duration of the ANF infusions. These changes were associated with a sustained fall in plasma volume but no activation of renin-angiotensin-aldosterone system. In contrast to the other actions, ANF-induced natriuresis, which was significant in the first 8 h of infusion, was not sustained. These studies show that significant biological effects occur in response to small ANF increments (20-25 pmol/l) and indicate that hemodynamic factors, especially fall in plasma volume, are important in determining the renal response even at near-normal plasma ANF concentrations.