The authors hypothesized that cerebral blood flow (CBF) changes will affect the dose of intracarotid propofol required to produce electrocerebral silence. The authors tested their hypothesis on New Zealand White rabbits. The first group of 9 animals received intracarotid propofol during (1) normoventilation, (2) hyperventilation, and (3) hypoventilation. The second group of 14 animals received intracarotid propofol with or without concurrent intraarterial verapamil, a potent cerebral vasodilator. The third group of 8 animals received bolus injection of propofol during normotension, during severe cerebral hypoperfusion, and after hemodynamic recovery. In the first group, there was a linear correlation between the dose of intracarotid propofol and percent change (%Delta) in CBF from the baseline due to changes in the minute ventilation, Total Dose (y) = 0.17 + 0.012 * %Delta CBF (x), n = 27, r = 0.76. In the second group, the dose of propofol was also a function of CBF change after verapamil, Total Dose (y) = 0.98 + 0.1 * %Delta CBF (x), n = 14, r = 0.75. In the third group, the duration of electrocerebral silence after intracarotid propofol (3 mg) was significantly increased with concurrent cerebral hypoperfusion compared with prehypoperfusion and posthypoperfusion values (141 +/- 38 vs. 19 +/- 24 and 16 +/- 12 s, respectively, P < 0.0001). The authors conclude that CBF affects the dose requirements of intracarotid propofol required to produce electrocerebral silence. Furthermore, the manipulation of CBF might be a useful tool to enhance the efficacy of intracarotid drugs.