The objective of the present study was to determine whether chronic salt load or depletion leads to adaptive changes in kinetics of atrial natriuretic factor (ANF) binding and/or responsiveness to ANF. We measured the equilibrium binding to and the steady-state dose-response effects of ANF1-28 on isolated kidneys from rats kept on a high (H) or low (L) salt diet for 15 days. 2. Twenty-four hour sodium excretion was 5.90 +/- 0.46 mEq for H vs 0.06 +/- 0.01 mEq for L (P less than 0.01). Plasma levels of immunoreactive ANF of H (42.2 +/- 3.9 pg/ml) were not significantly different from those for L (35.2 +/- 5.3 pg/ml). 3. There was no significant differences in distribution, apparent density or affinity of ANF specific binding sites determined in non-filtering isolated kidneys from rats kept on the H or L salt diet. 4. Dose-response curves for the hemodynamic and excretory effects of ANF1-28 in filtering isolated kidneys from rats kept on the H salt diet were not different from those of rats kept on the L salt diet. In contrast, the vasorelaxant response to ANF1-28 in isolated kidneys preconstricted by adding serum from 24-h nephrectomized rats to the perfusate (generation of angiotensin II) was significantly more pronounced in kidneys front rats chronically adapted to the high-salt diet. 5. This effect of ANF may contribute to the increased renal plasma flow and glomerular filtration rate occurring under conditions of chronic salt loading in intact animals.