The AT2 angiotensin II receptor selective ligand CGP42112 was radioiodinated and used to study AT2 receptor binding sites in the rat brain (combined olfactory bulb, septum, thalamus and midbrain) and whole adrenal. The [125I]CGP 42112 binding was of high affinity, saturable and specific in both tissues. Competition studies with nonselective and angiotensin II receptor subtype selective ligands, and evaluation of the effects of the sulfhydryl reducing agent beta-mercaptoethanol, confirmed that [125I]CGP 42112 bound selectively to the AT2 angiotensin II receptor subtype. [125I]CGP 42112 bound with higher affinity in the brain than in the adrenal. beta-Mercaptoethanol enhanced [125I]CGP 42112 binding in the brain, but did not alter its binding in the adrenal. A similar difference in binding affinity for [125I]sarcosine, isoleucine angiotensin II and enhancement of binding affinity by beta-mercaptoethanol was observed in the rat brain and adrenal. These observations suggest that the AT2 angiotensin II receptor subtypes in the brain and adrenal may differ.