The influence of isovolemic hemodilution with 6% hetastarch [hematocrits (Hct) ranging from 43 to 20%] on cerebral blood flow (CBF), cerebral red blood cell and plasma volumes, total cerebral blood volume (CBV), and cerebral Hct was examined in normothermic, normocarbic, halothane-anesthetized Sprague-Dawley rats. CBF was measured via the indicator-fractionation method ([3H]nicotine), red blood cell volume was measured using 99mTc-labeled red blood cells, while plasma volume was measured using [14C]dextran. Brain tissue was fixed in situ by microwave irradiation. All data plots (e.g., CBF vs. Hct) were fitted by linear regression methods. Hemodilution was associated with a progressive increase in forebrain CBF (from a fitted value of 78 ml.100 g-1.min-1 at Hct = 43%, to 171 ml.100 g-1.min-1 at 20%). Cerebral plasma volume also rose, while red blood cell volume decreased. Total CBV (i.e., the sum of red blood cell and plasma volumes) increased in parallel with CBF (from 2.51 ml/100 g at Hct = 43 to 4.94 ml/100 g at Hct = 20%). This increase is larger than can be explained by a simple increase in the diameter of arterial/arteriolar resistance vessels and may be due to either capillary recruitment or to an increase in the volume of postarteriolar structures. Calculated cerebral tissue hematocrit decreased. The magnitude of this decrease was larger than the reduction in arterial Hct; the ratio of cerebral to arterial Hct decreased from 0.780 at an arterial Hct equaling 43% to 0.458 at Hct equaling 20%.(ABSTRACT TRUNCATED AT 250 WORDS)