ABSTRACT. In order to determine the relative roles of O2 tension and content, C 0 2 tension, hydrogen ion concentration, arterial blood pressure, and cardiac output in the regulation of fetal cerebral blood flow (CBF), we used radioactively labeled microspheres to measure flow to 20 major brain regions in 24 chronically catheterized fetal lambs. We continually monitored fetal heart rate and blood pressure, and periodically measured arterial Po2, Pco2, pH, and hematocrit. In addition to CBF measurements during control periods, we measured CBF during: 1) hypoxia ( 0 2 content < 6 ml-dl-'; O2 tension c 15 torr) induced by having the ewe breathe a gas mixture with low 0 2 concentration, 2) hypercapnia (Pcoz > 50 torr) induced by increasing the maternal inspired COz, 3) acidosis and alkalosis (7.60 > pH > 6.60) induced by infusing lactic acid or bicarbonate into the fetus, and 4) hypotension (blood pressure < 35 mm Hg) and hypertension (blood pressure > 55 mm Hg) induced by rapidly phlebotomizing or transfusing the fetus. We used multiple regression analysis and analysis of covariance to examine the dependence of total cerebral blood flow on arterial O2 tension and content, COz tension, pH, blood pressure, and cardiac output. The results demonstrated that 1) fetal CBF increased linearly as oxygen tension or content decreased and a hierarchy of responsivity occurred (brainstem > subcortex and cortex), 2) fetal CBF increased as carbon dioxide tension increased with a different hierarchy of responsivity (brainstem > subcortex > cortex), and 3) autoregulation of fetal CBF over a wide range of blood pressure or cardiac output was maintained for both total CBF and the various brain regions examined. (Pediatr Res 18:1309-1316,1984 Abbreviations CBF, cerebral blood flow During the past several years, numerous investigators have used the radioactive microsphere technique to measure newborn and fetal cerebral blood flow in different species (1,19,24,25,36,40). In these studies, which have examined changes in flow as a function of changes in blood gas tensions, pH, and blood