BACKGROUND We hypothesized that the duration of electrocerebral (electroencephalogram, EEG) silence after bolus injection of propofol, a highly lipid soluble anesthetic drug, during transient cerebral hypoperfusion, will be directly related to the time taken by the bolus of drug to transit the cerebral circulation. METHODS We randomly divided 24 New Zealand White rabbits into two propofol volume groups: 0.5 and 0.8 mL groups. In each group, 12 animals received two intracarotid injections of 1% propofol: the first injection was made under normal physiological conditions and the second injection during cerebral hypoperfusion produced by bilateral carotid occlusion and IV bolus injection of adenosine and esmolol. We determined the duration of electrocerebral silence and the transit time of propofol emulsion under both cerebral circulation conditions. The transit time was measured by videomicroscopy through an implanted cranial window. RESULTS Cerebral hypoperfusion increased transit time with both low (2.3 +/- 0.7 to 55.7 +/- 21.4 s, n = 12, P < 0.0001) and high (2.2 +/- 0.6 to 62.5 +/- 31 s, n = 12, P < 0.0001) bolus volumes. The duration of electrocerebral silence during cerebral hypoperfusion was a function of the transit time with low (electrocerebral silence s = 152 + 2.3 x transit time, n = 12, r = 0.73, P = 0.007) and high (electrocerebral silence s = 186 + 3.2 x transit time, n = 12, r = 0.68, P = 0.02) bolus volumes. CONCLUSIONS These results suggest that manipulation of the transit time of highly lipid-soluble drugs profoundly enhances the effect site delivery.