Mechanical obstruction of the pulmonary artery causes an increase in right ventricular myocardial blood flow (MBF) proportional to the increased work load. This study was done to assess the response of MBF to hypoxia in the absence of mechanical obstruction of the right heart. The effects of hypoxia on cardiac performance and regional MBF were studied in 10 awake, unanesthetized dogs at 4,600 m (15,000 feet). Intracardiac pressures and pulmonary artery (PA) and thoracic aorta blood gases were recorded daily, initially at sea level and subsequently at 3,000 m and 4,500 m altitude. Regional MBF was measured on days 1 (control), 3, and 5 by use of 8 to 10 μ radioactive tracer microspheres, followed by postmortem assessment of subepicardial and subendocardial flow patterns in the left ventricle (LV), septum, and right ventricle (RV) (4,600 m). The results indicate that: (1) RV and PA pressures increase linearly with increasing degrees of hypoxia, (2) MBF increases in both the RV and LV with increasing degrees of hypoxia and elevated right-sided pressures, without increased systemic pressure, and (3) the transmural distribution of MBF is unaltered in both the BV and LV with altitude-induced hypoxia. These findings are distinctly different from those in which right-sided pressures are elevated secondary to mechanical obstruction of the PA in the absence of hypoxia.