We have previously shown that microinjection of monoclonal antibody to atrial natriuretic peptide (ANP) into the caudal nucleus tractus solitarii causes a pressor response in salt-sensitive spontaneously hypertensive rats (SHR) fed a basal (1%) salt diet, suggesting that endogenous ANP in this region may be involved in the centrally mediated regulation of blood pressure in this model. The present study tested the hypothesis that the pressor effect of blocking endogenous ANP in caudal nucleus tractus solitarii is enhanced by dietary salt supplementation in salt-sensitive SHR. Monoclonal antibody to ANP (0.55 μg) in 50 nl artificial cerebrospinal fluid or control immunoglobulin G was microinjected into the caudal nucleus tractus solitarii of conscious salt-sensitive SHR, salt-resistant SHR, and Wistar-Kyoto rats fed 1% or 8% salt diets for 3 weeks. Microinjection of the monoclonal antibody into the caudal nucleus tractus solitarii evoked similar increases in mean arterial pressure in salt-sensitive SHR on both 1% and 8% salt diets and in salt-resistant SHR on a 1% salt diet but had no effect in Wistar-Kyoto rats. In contrast, microinjection of control immunoglobulin G into this brain area did not alter mean arterial pressure or heart rate in any experimental group. Thus, endogenous ANP in caudal nucleus tractus solitarii mediates tonic control of blood pressure in both salt-sensitive and salt-resistant SHR but not in Wistar-Kyoto rats, and this effect is independent of the salt sensitivity of hypertension and of dietary salt intake.