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 eight 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 to 60% of maximum. CONCLUSION This study supports hypoglossus nerve stimulation as a treatment option for obstructive sleep apnea.