Brain Angiotensin II, through stimulation of brain AT₁ receptors, regulates pituitary hormones and autonomic activity. We have administered the insurmountable AT₁ antagonist Candesartan, s.c. via osmotic minipumps for 14 days, to determine whether peripheral chronic AT₁ blockade affects AT₁ receptor binding and mRNA in the brain. Peripherally administered Candesartan (0.1, 0.5 or 1.0 mg/kg per day) inhibits AT₁ binding in adrenal gland zona glomerulosa and kidney glomeruli. In addition, Candesartan dose-dependently decreases AT₁ binding in brain areas outside (subfornical organ and area postrema) and inside (paraventricular nucleus of the hypothalamus and nucleus of the solitary tract) the blood–brain barrier. Conversely, peripheral treatment with Candesartan does not affect AT_1A receptor mRNA, the predominant receptor subtype expressed in these areas, or Angiotensin II binding to AT₂ receptors in the locus coeruleus or inferior olive. Our results demonstrate that chronic peripheral treatment with selective, potent AT₁ antagonists not only inhibits peripheral but also brain AT₁ receptors. These central effects may play a role in the antihypertensive effects of the AT₁ antagonist Candesartan.