In the search for central actions of hydrochlorothiazide (HCTZ), the drug was injected directly into the hypothalamus (HTH) of hypertensive rats. This caused regular fall of blood pressure (BP) and development of a flat dose-response curve-both events resembling corresponding phenomena in systemic injections. In a small number of experiments, the drug caused a rise in BP. This result was enhanced when normotensive rats were injected into the HTH. It is concluded that the rat HTH bears two antagonistic receptors for HCTZ.