The cerebrovasculature dilates or constricts in response to acute blood pressure changes to stabilize cerebral blood flow across a range of blood pressures. It is unclear, however, whether such dynamic cerebral autoregulation (dCA) is equally effective in responding to falling versus rising blood pressure. In this study we applied a pharmacological approach to evaluate dCA gain to transient hypotension and hypertension and compared this method with 2 established indices of dCA that do not explicitly differentiate between dCA efficacy and falling versus rising blood pressure. Middle cerebral arterial velocity and blood pressure recordings were made in 26 healthy volunteers randomized to 2 protocols. In 10 subjects, dCA gain to transient hypotension induced with intravenous nitroprusside was compared with dCA gain to transient hypertension induced with intravenous phenylephrine. In 16 subjects, dCA gain to transient hypotension induced with intravenous nitroprusside was compared with the rate of regulation and autoregulatory index derived from transient hypotension induced with the thigh cuff deflation technique. dCA gain to transient hypotension induced with intravenous nitroprusside was unrelated to dCA gain to transient hypertension induced with intravenous phenylephrine (r=0.06; P=0.87) and was consistently greater than dCA gain to transient hypertension induced with intravenous phenylephrine (0.57+/-0.16 versus 0.31+/-0.20 cm/s per millimeter of mercury; P<0.01). However, dCA gain to transient hypotension induced with intravenous nitroprusside was inversely related to the rate of regulation (r=-0.52; P=0.037) and autoregulatory index (r=-0.66; P=0.005). These data indicate that, under our laboratory conditions, dCA appears to be inherently nonlinear with disparate efficacy against rising and falling blood pressure, and dCA gain derived from pharmacologically induced transient hypotension correlates with established nonpharmacological indices of dCA.