The ventilatory effects of graded reductions in brain bloow flow (BBF) were studied in unanesthetized goats. At a BBF of 85% of control (PVO2 = 29.2 Torr, PVCO2 = 47.3 Torr) there were no clear ventilatory effects. At BBF of 70% of control (PVO2 = 25.2, PVCO2 = 50.5) and 50% of control (PVCO2 = 22.3, PVCO2 = 53.0) there was hyperpnea, due primarily to an increase of tidal volume. Further reduction of BBF (avg of 42% of control) first produced intense tachypnea and then (30--40% of control) caused apnea that was reversible. At 50% BBF there was a reduction of brain O2 consumption, (4.67--4.00 ml/min) and an increase in systemic O2 consumption. beta-Adrenergic blockade prevented the increase in systemic O2 consumption and reduced the hyperpnea by two-thirds at 50% BBF; the residual hyperpnea was associated with hypocapnia in contrast to the hyperpnea prior to beta-adrenergic blockade, which was virtually isocapnic. The data suggest that hyperpnea due to brain ischemia is a result of both brain acidosis and systemic hypermetabolism. The similarity of the pattern of responses to that previously reported for progressive carboxyhemoglobinemia suggests that brain hypoxia is a determinant of the ventilatory responses to brain ischemia.