The goal of this study was to determine whether periodic breathing (PB), which is highly prevalent during sleep at high altitudes, imposes physiological penalties on the respiratory system in the absence of any accompanying disease. Using a computer model of respiratory gas exchange, we compared the effects of a variety of PB patterns on the chemical and mechanical costs of breathing to those resulting from regular tidal breathing. Although PB produced considerable fluctuation in arterial blood gas tensions, for the same cycle-averaged ventilation, higher arterial oxygen saturation and lower arterial carbon dioxide levels were achieved. This result can be explained by the fact that the combination of large breaths and apnea in PB leads to a substantial reduction in dead space ventilation. At the same time, the savings in mechanical cost achieved by the respiratory muscles during apnea partially offset the increase during the breathing phase. Consequently, the "pressure cost," a criterion based on mean inspiratory pressure, was elevated only slightly, although the average work rate of breathing increased significantly. We found that, at extreme altitudes, PB patterns with clusters of 2 to 4 large breaths that alternate with apnea produce the highest arterial oxygenation levels and lowest pressure costs. The common occurrence of PB patterns with closely similar features has been reported in sleeping healthy sojourners at extreme altitudes. Taken together, these findings suggest that PB favors a reduction in the oxygen demands of the respiratory muscles and therefore may not be as detrimental as it is generally believed to be.