BACKGROUND: Hemodilution may increase cerebral blood flow (CBF) but the mechanism(s) remain controversal. Autoregulation is easily modified or disturbed by several conditions. The aim of this study was to evaluate the effects of isovolemic hemodilution on the autoregulation of cerebral blood flow in a rabbit model. METHODS: Stepwise hemodilution was accomplished by incrementally removing whole blood from the animals in amounts of 8-12 ml and replacing this with an equal volume of 6% hetastarch in saline. This procedure was continued until the target content values of approximately Hct -18% were achieved. To evaluate the influence of pressure changes on CBF, mean arterial pressure (MAP) was increased from a baseline pressure (approximately 78 mmHg) to 145 mmHg by infusing methoxamine, and cerebral blood flow was measured at each MAP level using the hydrogen clearence method after MAP had been stabilized for 15 min. RESULTS: Stepwise hespen replacement caused a sudden drop of Hct from 37.4% to 18.5% and a simultaneously a significant increase in local CBF of 161% in the hemodilution group. Hemodilution significantly reduced CaO2 in the hemodilution group (9.45 +/- 1.7 ml O2/dl) versus the control group (18.34 +/- 1.3 ml O2/dl). However, despite these decrease in CaO2, calculated cerebral oxygen delivery (DO2) was as well maintained in the hemodilution group (22.47 +/- 7.28 ml O2/100 gm/min) as in the control group (24.14 +/- 8.67 ml O2/100 gm/min). MAP increases from 78 mmHg to 145 mmHg produced a significant increase in CBF from 122.4 +/- 32.8 ml/100 gm/min to 170.9 +/- 23.7 ml/100 gm/min in control group (39.6%) and from 218.4 +/- 75.6 ml/100 gm/min to 268.4 +/- 106.5 ml/100 gm/min in the hemodilution group (44.6%) (P<0.001). These CBF increases were not significantly different in the two groups. CONCLUSIONS: The present study demonstrates that in the normal brain the decrease in CaO2 caused by hemodilution is well compensated for by an increase CBF, and that oxygen transport to the brain is also well maintained during at a Hct value of 20%. Although the present study did not show the tight CBF control within the MAP range from 78 mmHg to 145 mmHg, hemodilution did not alter the response of the cerebral circulation to increased MAP.