Metabolic acidosis in the neonate is often secondary to hypoxemia and cardiopulmonary disturbances. Sodium bicarbonate, an agent used to treat metabolic acidemia in newborns, is often administered during hypoxemia. In the absence of acid-base alterations, during hypoxemia a reciprocal relationship exists between arterial O2 content (CaO2) and brain blood flow (BBF). However, when hypoxemia is compounded by acidemia it is unclear whether the increase in arterial pH achieved by infusions of sodium bicarbonate alters BBF. To investigate this, BBF (microsphere technique), arterial blood gases, and CaO2 were measured in 14 ventilated piglets. Variables were assessed during a control period, a period of hypoxemia (50 min) associated with metabolic acidemia (hypoxemia + acidemia), and after infusions of either saline (n = 6) or NaHCO3 (n = 8, 2 mEq/kg) during continued hypoxemia. Arterial pH was similar in both groups at control, and hypoxemia + acidemia resulted in comparable reductions of pH in both saline- and NaHCO3-treated piglets (7.21 +/- 0.02 versus 7.21 +/- 0.03, respectively). NaHCO3 infusions produced a significant rise in pH, 7.30 +/- 0.03 versus 7.15 +/- 0.03, p less than 0.05. In each group CaO2 paralleled changes in pH but did not differ between groups. In all animals BBF increased more than 2-fold during hypoxemia + acidemia and was unaltered by infusions of either saline or NaHCO3. Brain O2 delivery decreased in both groups during hypoxemia + acidemia and was unchanged by infusions of saline or NaHCO3. During hypoxemia + acidemia the change in arterial pH induced by NaHCO3 (2 mEq/kg) does not alter BBF or brain O2 delivery.