The aim of this study was to ascertain whether drug-induced cholinergic hypofunction in the posterior hypothalamus would affect the development and the maintenance of hypertension in hypertensive rats. Spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats were treated with AF64A, a neurotoxin which can irreversibly inhibit cholinergic transmission in vivo. AF64A or saline was injected bilaterally into the posterior hypothalamus of rats of two age groups: normotensive one month-old rats whose blood pressure was subsequently measured at the age of three months and hypertensive three month-old rats, whose blood pressure was measured four weeks later. In both age groups there was a significant fall in mean arterial blood pressure in SHR but not WKY rats. In SHR injected at the age of one month, there was a fall of at least 15.9 mm Hg, while in the rats injected at the age of three months there was a fall of 14.3 mm Hg. Heart rate in either strain was not affected. When AF64A was injected into the anterior hypothalamus of one month-old SHR, no antihypertensive effect was observed in these rats at the age of three months. These results show that cholinergic stimulation in the posterior hypothalamus may play a role in both the development and maintenance of hypertension in SHR.