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Cerebral blood flow (CBF) falls as hematocrit (Hct) rises. Investigators have differed on the relative importance of the increases in arterial O2 content (CaO2) and red blood cell concentration in mediating the fall. Our experimental protocol attempted to determine the independent effects of these two variables. In 13 unanesthetized lambs (less than 7 days old) we measured arterial and sagittal sinus blood gases, and O2 contents, and CBF (microsphere technique) at oxyhemoglobin Hcts of approximately 20 and 40% and after an isovolemic exchange transfusion with a mixture of normal and pure methemoglobin (MHb) containing red cells. Following MHb exchange, Hct rose (19.7 +/- 0.3 vs. 38.2 +/- 0.4%, mean +/- SEM) with little change in CaO2 (9.3 +/- 0.2 vs. 10.0 +/- 0.3 vol%). Arterial PCO2, pH, mean arterial blood pressure, and cerebral O2 consumption (CMRO2) did not change. However, CBF fell (153 +/- 11 vs …