Previous studies using an Induction‐Delay‐Expression (I‐D‐E) experimental design have demonstrated that one‐week ANG II pre‐treatment can sensitize the brain to produce an enhanced hypertensive response to subsequent ANG II. It has been shown that estrogen can act through the CNS to attenuate ANG II hypertension. The present study was to test whether there is a sex difference in the sensitizing effects of ANG II and the involvement of central estrogen in this sensitization process. Male, intact and ovariectomized (OVX) female rats were implanted for telemetered blood pressure (BP) recording. During I low doses of ANG II alone or concurrent administration with icv estrogen was given for 1 week. After1 week (D) rest, slow pressor doses of ANG II was given for 2 weeks (E).In males and OVX females, ANG II had no sustained effect on BP during I and D. However, during E ANG II‐induced hypertension was greater in the groups receiving ANG II during I in comparison to those groups receiving vehicle. Central administration of estrogen during I blocked low dose of ANG II‐induced sensitization. In intact females, low dose of ANG II actually induced a decrease in BP during I and D. Subsequent high doses of ANG II during E did not result in an enhanced increase in BP in either group. The results indicate that estrogen can play a protective role during the sensitization process and attenuate the development of ANG II‐induced hypertension.