The effect of vagal reflexes on bronchomotor tone can be altered by their interaction with other bronchomotor factors, such as the prevailing state of oxygenation. In anesthetized, paralyzed, and artificially ventilated dogs, a reflex constriction was induced in an isolated tracheal segment by administration of aerosolized histamine to the lungs. When the challenge was repeated during hypoxic conditions (PaO2, 45 mmHg), the magnitude of the reflex response was significantly larger than during normoxia. In contrast, during hyperoxia (PaO2, 344 mmHg), the response was significantly smaller than the normoxic response. The changes in the prevailing state of oxygenation were done under isocapnic and isohydric conditions. Hyperoxia alone had no effect upon baseline bronchomotor tone, whereas hypoxia caused an increase in baseline tone in approximately half the animals. The effect of hypoxia upon the reflex response to histamine was not affected by the baseline changes. We think that the potentiating effects of hypoxia and the attenuating effects of hyperoxia are mediated by an interaction between lung sensory receptors and carotid body chemoreceptors.