The interaction of chemoreflex and pulmonary inflation reflex control of the coronary circulation was examined in conscious dogs by comparing the responses to chemoreflex stimulation (intracarotid injection of nicotine) when ventilation was allowed to increase with those when ventilation was controlled. The responses were also compared with those elicited by both forced mechanical and spontaneous hyperinflation. When the heart rate was constant, intracarotidly administered nicotine induced an increase in the depth of respiration followed closely by an increase in late diastolic coronary flow from 48 +/- 2 to 106 +/- 8 ml/min and a reduction in late diastolic coronary resistance from 1.62 +/- 0.08 to 0.78 +/- 0.06 mm Hg/ml min-1. After beta-receptor and cholinergic blockade, a similar coronary dilation in response to nicotine occurred only when ventilation was allowed to increase. However, when ventilation was controlled, intracarotidly administered nicotine increased coronary resistance after combined beta-receptor and cholinergic blockade. The reflex coronary dilation was not observed after carotid sinus nerve section or after alpha-receptor blockade. Thus, nicotine stimulation of the carotid chemoreflex results in a striking coronary dilation that has two components. The minor component involves a chemoreflex with its efferent pathway in tthe vagi. The major component of coronary dilation follows an increase in the depth of respiration, and its efferent component appears to involve withdrawal of alpha-adrenergic constrictor tone. An almost identical period of reflex coronary dilation followed either forced mechanical or spontaneous hyperinflation in the conscious dog.