Interactions between internal and external O2 stimulus levels were assessed by measuring the ventilatory and cardiovascular responses to varying water (PWO2) and air bladder (PabO2) O2 levels and intravascular NaCN in anesthetized spontaneously ventilating Lepisosteus osseus. As PWO2 fell, air-breathing frequency (fab) increased. Buccal pressure amplitude (Pb) also increased as PWO2 fell from hyperoxia to normoxia, but hypoxic water depressed Pb. The PO2 in the ventral aorta (VA) fell as PabO2 fell, which stimulated fab and Pb when the gar was in normoxic or hyperoxic water. Thus gill ventilation and air breathing were normally controlled by both internal and external O2 levels, but aquatic hypoxia uniformly depressed gill ventilation regardless of changes in PabO2 levels. Heart rate and blood pressure were unaffected by these changes. NaCN stimulated hypoxic reflexes and bradycardia more quickly when given into the VA or conus than when given into the dorsal aorta. The animals appear to possess internal chemoreceptors that set the level of hypoxic drive and external chemoreceptors that inhibit gill ventilation and shift the ventilatory emphasis from water to air breathing.