Our previous studies demonstrated that chronic dietary NaCl suplementation is associated with significant increases in plasma atrial natriuretic factor in Wistar-Kyoto (WKY) rats but not in NaCl-sensitive spontaneously hypertensive rats (SHR-S). The current study tested the hypotheses that 1) acute volume-induced atrial natriuretic factor release is impaired in SHR-S compared with control NaCl-resistant SHR (SHR-R) and WKY rats maintained on basal (1%) NaCl diets; 2) dietary NaCl supplementation (8% NaCl for 2 weeks) alters acute volume-dependent atrial natriuretic factor release in these strains; and 3) replacement of the deficiency in circulating atrial natriuretic factor seen in NaCl-supplemented SHR-S can reverse the NaCl-sensitive component of hypertension. SHR-S and control SHR-R and WKY rats were placed on 1% or 8% NaCl diets at age 7 weeks; 2 weeks later, right atrial pressure and plasma atrial natriuretic factor were measured in conscious rats before and after acute volume expansion (7, 20, and 60 ml/kg, 5% dextrose, for 1 minute). The slopes of the right atrial pressure x plasma atrial natriuretic factor linear regression for the SHR-S fed both 1% and 8% NaCl were significantly shallower (p < 0.01) than those of 1% NaCl-fed SHR-R or WKY rats. Dietary NaCl supplementation did not alter right atrial pressure in any strain and blunted acute volume-induced atrial natriuretic factor release in WKY rats, but not in SHR-S or SHR-R, suggesting the dietary NaCl-induced elevation in plasma atrial natriuretic factor levels in WKY rats may be related to impaired clearance, as well as enhanced release, of the peptide. The plasma levels of exogenous atrial natriuretic factor required to abolish the NaCl-induced pressor effect in SHR-S were 12-fold greater than endogenous plasma atrial natriuretic factor levels in 8% NaCl-fed WKY rats, suggesting that impairment of atrial natriuretic factor release does not play a major role in the pathogenesis of NaCl-sensitive hypertension in SHR-S.