The effects of increased intracranial pressure (ICP) and increased cardiac output (QT) on the pulmonary vascular response to regional alveolar hypoxia were compared in pentobarbital-anesthetized, closed-chested dogs. A bronchial divider was inserted, the right lung (RL) was continuously ventilated with 100% O2, and the left lung (LL) was ventilated with either 100% O2 (hyperoxia) or a hypoxic gas mixture (hypoxia). Sulfur hexafluoride (SF6) was used to measure differential lung blood flow and the multiple inert gas technique assessed gas exchange. The response to LL alveolar hypoxia (hypoxic pulmonary vasoconstriction, HPV) was studied in each animal prior to, during, and after the ICP was increased by infusing mock cerebrospinal fluid (CSF) into a lateral ventricle so that cerebral perfusion pressure was 25 mmHg. During both control periods, QT was randomly altered by opening (high QT) or closing (normal QT) two arteriovenous fistulas. Increasing ICP significantly increased QT (P less than 0.01), pulmonary artery pressure (PAP) (P less than 0.05), and mixed venous oxygen tension (PVO2) (P less than 0.05), compared with normal QT controls. Opening the arteriovenous fistulas achieved similar increases in QT (P less than 0.01), PAP (P less than 0.05), and PVO2 (P less than 0.05). The percentage of blood flow to the LL (QL/QT%) during hyperoxia was 43.9 +/- 0.8% (mean +/- SE) and did not vary with manipulation of QT or ICP. QL/QT% during LL hypoxia was significantly increased by both increased ICP (24.6 +/- 3.5%) and high QT (23.1 +/- 1.0%) compared with normal QT (16.8 +/- 2.1) controls (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)