In 4 unsedated, exercising dogs, we studied the effects of inhaled histamine aerosol on minute volume of ventilation, respiratory frequency, tidal volume, total pulmonary resistance, and dynamic pulmonary compliance. Inhalation (5 breaths) of 1 to 2 per cent histamine aerosols increased minute ventilation (mean, 50 per cent; p less than 0.001) by increasing respiratory frequency (mean, 166 percent; P less than 0.001), despite decreasing tidal volume (mean, 42 percent; P less than 0.0001). Total pulmonary resistance increased (mean, 200 per cent; P less than 0.001.) Breathing supplemental O2 did not affect the ventilatory response to histamine. Adding external resistive loads to a dog's airway did not simulate the pattern of rapid, shallow breathing produced by histamine. Inhalation of terbutaline prevented the changes in total pulmonary resistance and dynamic pulmonary compliance but did not alter the ventilatory response to histamine. When conduction in the cervical vagus nerves (which were implanted chronically in skin loops) was blocked by cooling, the ventilatory response to histamine was abolished. We concluded that histamine stimulates breathing by stimulation of receptors whose afferent pathways are in the vagus nerves; the effective stimulus is not bronchoconstriction but is presumably due to direct stimulation of airway receptors.