Rationale: Anesthesia-induced uncoupling of upper airway dilating and inspiratory pump muscles activation may cause inspiratory flow limitation, thereby mimicking obstructive sleep apnea/hypopnea. Objectives: Determine whether inspiratory flow limitation occurs in spontaneously breathing anesthetized rabbits and whether this can be reversed by direct hypoglossal nerve stimulation and by the application of continuous positive airway pressure. Methods: Ten New Zealand white rabbits were anesthetized, instrumented and studied supine while breathing spontaneously at ambient pressure or during the application of positive or negative airway pressure. Under each of these conditions, the effect of unilateral or bilateral hypoglossal nerve stimulation was investigated. Measurements: Inspiratory flow and tidal volume were measured together with esophageal pressure and the electromyographic activity of diaphragm, alae nasi and genioglossus muscles. Main results: Anesthesia caused a marked increase in inspiratory resistance, snoring and in 8 rabbits, inspiratory flow limitation. Hypoglossus nerve stimulation was as effective as continuous positive airway pressure in reversing inspiratory flow limitation and snoring. Its effectiveness increased progressively as airway opening pressure was lowered, reached a maximum at -5 cm H₂O, but declined markedly at lower pressures. With negative airway opening pressure, airway collapse eventually occurred during inspiration that could be prevented by hypoglossus nerve stimulation. The recruitment characteristics of hypoglossus nerve fibers was steep, and significant upper airway dilating effects already obtained with stimulus intensities 36-60% of maximum. Conclusion: This study supports hypoglossus nerve stimulation as a treatment option for obstructive sleep apnea.