To determine whether stimulus frequency affects physiological compensation to an intermittent respiratory stimulus we studied piglets (n=43) aged 14.8 ± 2.4 days. 24-min total hypercapnic-hypoxia (HH) (10% O₂/ 6% CO₂/ balance N₂ = HH) was delivered in 24-, 8-, 4-, or 2-min cycles alternating with air. Controls (n=10) breathed air continuously. Minute ventilation and temperature were not different between the 2-min and 24-min groups, with neither different to controls during recovery. Piglets exposed to 8-min cycles had ventilatory stimulation whereas those exposed to 4-min cycles had significant depression of ventilation. Despite this, piglets in these intermediate IHH groups (8- and 4-min cycles) showed more severe acidosis, and attenuated temperature changes (P <0.001 and <0.01 for pH and temp vs 24-min, respectively). Cycle time affected the ability of young piglets to tolerate IHH. More severe respiratory acidosis developed when IHH was delivered in intermediate (4-min, or 8-min) cycles compared to the same total dose as a single episode or in short (2-min) cycles.