Previous studies have shown that microinjection of atrial natriuretic peptide into the caudal nucleus tractus solitarii produces significant increases in local neuronal firing rate associated with reductions in arterial pressure in anesthetized Wistar rats. Single units excited by microinjection of atrial natriuretic peptide into the caudal nucleus tractus solitarii were also excited by activation of arterial baroreceptors and inhibited by baroreceptor unloading. To test the hypothesis that endogenous atrial natriuretic peptide in caudal nucleus tractus solitarii is involved in the tonic control of blood pressure in the rat, we administered a blocking monoclonal antibody to atrial natriuretic peptide in a volume of 50 nl artificial cerebrospinal fluid via microinjection into the caudal nucleus tractus solitarii of spontaneously hypertensive and Wistar-Kyoto rats and observed the effects on mean arterial pressure and heart rate. Control injections of monoclonal antibody were administered into the rostral nucleus tractus solitarii, hypoglossal nucleus, spinal trigeminal nucleus, and cuneate nucleus of spontaneously hypertensive rats. Microinjection of monoclonal antibody into the caudal nucleus tractus solitarii caused significant increases in mean arterial pressure in spontaneously hypertensive rats but not in Wistar-Kyoto rats. There was no concomitant change in heart rate. Control injections of purified mouse immunoglobulin into the caudal nucleus tractus solitarii and of monoclonal antibody into the control neuronal groups listed above had no effect on mean arterial pressure. These results suggest that endogenous atrial natriuretic peptide in the caudal nucleus tractus solitarii mediates tonic control of blood pressure in spontaneously hypertensive rats but not in normotensive Wistar-Kyoto rats.