Nine adult patients with obstructive sleep apnea syndrome were administered medroxyprogesterone acetate, 60 to 120 mg/day, and the effect of medroxyprogesterone on clinical symptoms and obstructive apneas during sleep was assessed. Four patients responded with resolution of daytime sleepiness, disappearance of pedal edema, and a decrease in the number of obstructive apneas during sleep. Cessation of therapy led to a return of daytime sleepiness in three and an increase in obstructive apneas in all four subjects. Two responders experienced side effects of alopecia or decreased libido. Before medroxyprogesterone therapy, responders were distinguished from nonresponders only by the presence of a significantly lower resting arterial oxygen tension during wakefulness. We characterize a subgroup of patients who benefit from medroxyprogesterone therapy by reducing obstructive apneas during sleep.