In order to determine the relative roles of O2 tension and content, CO2 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 (O2 content less than 6 ml X dl-1; O2 tension less than 15 torr) induced by having the ewe breathe a gas mixture with low O2 concentration, 2) hypercapnia (PCO2 greater than 50 torr) induced by increasing the maternal inspired CO2, 3) acidosis and alkalosis (7.60 greater than pH greater than 6.60) induced by infusing lactic acid or bicarbonate into the fetus, and 4) hypotension (blood pressure less than 35 mm Hg) and hypertension (blood pressure greater than 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, CO2 tension, pH, blood pressure, and cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)