Hypoglossal nerve stimulation was investigated as a method to relieve an induced upper airway obstruction. Six dogs were implanted with a cuff electrode applied to each hypoglossal nerve and a pulse generator. After 4 weeks, the hypoglossal nerve was stimulated (50% duty cycle) for up to 8 weeks. At 12 weeks a double tracheotomy was placed, with a negative pressure intermittently applied to the upper limb, simulating inspiratory airway pressure. Unilateral hypoglossal nerve stimulation improved peak upper airway flow from an average of 0.1 L/s to 1.6 L/s (P = 0.0001). Seventy-seven percent of the maximum possible flow (explanted tracheotomy tube) was obtained with unilateral stimulation. Histopathological evaluation revealed no nerve damage secondary to chronic stimulation. This study provides support for clinical trials of hypoglossal stimulation for obstructive sleep apnea.