Background and Purpose We attempted to clarify the role of the acetazolamide-reactive mechanism in cerebral hemodynamic autoregulation and to establish a useful method of estimation using the acetazolamide test. Methods We examined 18 patients whose cerebral hemodynamics were considered to be normal and whose cerebral blood flow (CBF) was maintained during the balloon occlusion test (BOT) of the internal carotid artery. We measured the mean stump pressure (MSTP) and the mean CBF in the middle cerebral arterial territory using a xenon-enhanced CT system during BOT with and without acetazolamide activation. We obtained the asymmetry ratio (AR=occluded CBF/contralateral CBF) and the increased CBF parameters caused by acetazolamide activation expressed as an absolute value (Delta CBF) and a percentage (%Delta CBF) for the occluded side. Results AR during BOT with and without acetazolamide activation differed significantly (P<.001, paired t test) despite the lack of significant MSTP changes. Furthermore, although there was no significant correlation between MSTP and AR without acetazolamide activation, a positive significant correlation was detected with acetazolamide activation (r=.634, P=.005, linear regression analysis). There were significant correlations between Delta CBF and MSTP (r=.574, P=.013) and %Delta CBF and MSTP (r=.640, P=.004). Conclusions We consider that the acetazolamide-reactive mechanism functions as autoregulation at the lower end of the autoregulatory range. The acetazolamide Lest, using %Delta CBF or Delta CBF as parameters (which both directly reflect MSTP), is useful for estimating the cerebral perfusion pressure decrease and presence of hemodynamic compromise.