Cerebral blood volume (CBV = cerebral plasma volume [CPV] + cerebral red cell volume [CRBCV]) is one determinant of intracranial pressure. In an effort to quantitate the effects of anesthetics and Paco2on CBV, the authors measured cerebral plasma volume (CPV) in normocapnic (Paco2≈ 42 mmHg) and hypocapnic (Paco2= 22 mmHg) rats receiving 1 MAC doses of isoflurane or halothane, or given an approximately equivalent dose of pentobarbital. All animals were paralyzed, their lungs mechanically ventilated, and body temperature kept normal throughout the study. CPV was measured using14C-labeled dextran, a large (70,000 molecular weight [M.W.]), nondiffusible compound that was given intravenously and allowed to circulate for ≈5 min. The experiments then were terminated by freezing the brainsin situwith liquid N2poured into a funnel affixed to the exposed calvarium. Isotope concentrations in solubilized brain and in plasma were determined by scintillation counting, and CPV was calculated as the ratio between these values. CPV during both hypocapnic and normocapnic pentobarbital anesthesia was less than with either volatile agent. During normocapnia, CPV for pentobarbital = 2.1 ± 0.26 ml/100 g (mean ± SD, n = 8), compared with 2.96 ± 0.44 ml/100 g (n = 9) and 3.06 ± 0.44 ml/100 g (n = 9) for halothane and isoflurane, respectively. There were no differences in CPV between the two volatile agents during normocapnia. However, during hypocapnia, CPV in isoflurane-anesthetized animals decreased to 2.29 ± 0.43 ml/100 g, as compared with 2.68 ± 0.36 ml/100 g with halothane (P< 0.05) and 1.86 ± 0.33 ml/100 g for pentobarbital (not significantvs.isoflurane,P< 0.01 for pentobarbitalvs.halothane). The magnitude of these differences—particularly the changes produced by Paco2—appears to be smaller than previously published differences in cerebral blood flow (CBF), which supports suggestions that it may be invalid to equate changes in CBF with changes in brain blood volume or intracranial pressure.