Periodic breathing is a commonly observed in chronic heart failure (CHF) when pulmonary capillary wedge pressure is abnormally high and there is usually concomitant tachypneic hyperventilation. We hypothesized that acute pulmonary hypertension at pressures encountered in CHF and involving all of the lungs and pulmonary vessels would predispose to apnea/unstable breathing during sleep. We tested this in a chronically instrumented, unanesthetized dog model during NREM sleep. Pulmonary hypertension was created by partial occlusion of the left atrium by means of an implanted balloon catheter in the atrial lumen. Raising mean left atrial pressure by 5.7 ± 1.1 Torr resulted immediately in tachypneic hyperventilation (breathing frequency increased significantly from 13.8 to 19.9 br/min; PETCO₂ fell significantly from 38.5 to 35.9 Torr). This tachypneic hyperventilation was present during wakefulness, NREM, and REM sleep. In NREM sleep, this increase in left atrial pressure increased the gain of the ventilatory response to CO₂ below eupnea (1.3 to 2.2 1 /min /Torr) and thereby narrowed the CO₂ reserve (PETCO_{2 apneic threshold} - PETCO_{2 eupnea}) despite the decreased plant gain resulting from the hyperventilation. We conclude that acute pulmonary hypertension during sleep results in a narrowed CO₂ reserve and thus predisposes toward apnea/unstable breathing and may therefore contribute to the breathing instability observed in CHF.