The pressor response to 5-hydroxytryptamine (5-HT), norepinephrine (NE), and KCI was studied in the blood- and Ringer's- perfused hindquarters of the spontaneously hypertensive rat (SHR) and the Kyoto normotensive Wistar rat in two age groups: 8 to 10 weeks and 6 to 8 months. In both preparations, the response to 5-HT, NE and KCI was greater in the young and old SHRs than in the age-matched normotensive Wistar rats. The enhanced responsiveness to 5-HT in old SHRs was of greater magnitude than that to NE or KCI, whereas in young SHRs the enhanced responsiveness to the three pressor agents was of similar magnitude. This appears to be due in part to a greater reduction in responsiveness to NE and KCI than to 5-HT as the animal becomes older. Enhanced responsiveness to 5-HT also occurs in the renal hypertensive rat. However, there was no difference in responsiveness to low doses of NE or KCI in the renal hypertensive rat. The response to 5-HT in the old SHR was blocked by methysergide but was not affected by phentolamine, isoproterenol or nitroglycerin. In the old SHR made hypotensive by occlusion of the abdominal aorta for a duration of 3 to 5 weeks, the responsiveness to all three pressor agents was reduced but was most marked for 5-HT. These latter results suggest that blood pressure per se contributes to the enhanced responsiveness to NE, KCI and, to a greater extent, 5-HT.