Although patients using transtracheal oxygen (TTO2) frequently report decreased dyspnea and improved exercise tolerance, the mechanism for these effects is unknown. We hypothesized that these patients might have decreased inspired minute ventilation (Vi), and this might be one mechanism for their decreased dyspnea and improved exercise tolerance. The effects of TTO2 on Vi were studied in seven patients with chronic hypoxemia; two had chronic obstructive lung disease and five had severe restrictive disorders. Vi, exhaled minute ventilation (Ve), respiratory rate (RR), tidal volume (Vt), earlobe O2 saturation (O2 sat), and arterial blood gases were measured while patients received varying amounts of oxygen either transtracheally or by mouth to achieve equivalent degrees of oxygenation. With TTO2 Vi was reduced compared to Vi with mouth O2 at similar levels of PaO2. As TTO2 flow rate increased, Vi decreased; at 6 L/min O2 delivered transtracheally, mean Vi was reduced by 54 ± 7.0%. Reduction in Vi was due to decreased Vt; RR did not change. To determine if air delivered transtracheally decreased Vi, five patients were studied while receiving air transtracheally or by mouth. With transtracheal air, Vi was significantly less than Vi obtained while breathing air by mouth. We conclude that Vi is decreased when oxygen or air is delivered directly into the trachea and that Vi decreases as transtracheal flow increases. This effect is not due solely to changes in oxygenation. Decreased dyspnea and improved exercise tolerance in patients using TTO2 may be due to decreased Vi and decreased inspiratory work of breathing.