Background: Both hypertension and high blood pressure variability (BPV) are involved in cardiovascular damage. This comparative study was designed to explore the possible effects of both of these phenomena on the cardiovascular system. Methods: The high BPV model of 16-week sinoaortic denervated (SAD) rats and the hypertension model of spontaneously hypertensive rats (SHR) were used for comparison at the same age of 26 weeks. The comparison was focus on hemodynamics, cardiovascular hypertrophy, and hemodynamic responses to ketanserin. Linear regression analysis was performed to study the role of hemodynamics in cardiovascular hypertrophy. Results: In SHR, hypertension was accompanied by a moderately high BPV, whereas in SAD rats, substantially high BPV existed alone, without hypertension. Left ventricular hypertrophy was severe in SHR but was mild in SAD rats. Aortic hypertrophy was present in SAD rats but was absent in SHR. In SAD rats, the hypertrophy was correlated with BPV but not with blood pressure (BP) level. However, in SHR, hypertrophy was correlated with both BP and BPV level. The BP-lowering effect of ketanserin was comparable in both models, whereas its BPV-lowering effect was greater in SAD rats than in SHR. This hypersensitivity was associated with basal BPV level in SAD rats. Conclusions: These results indicate that hypertension may be more important than high BPV in causing left ventricular hypertrophy, and that the aorta may be more sensitive to substantially high BPV.