Seven morbidly obese patients with sleep-related upper airway obstruction (UAO) were studied before and during progesterone treatment. All subjects had severe daytime somnolence, and five of the seven had congestive heart failure. All subjects were studied for one or two consecutive baseline nights in the sleep laboratory. Six of the seven subjects showed a mean of greater than 100 UAOs. Patients were treated for two to four weeks with medroxyprogesterone acetate, 20 mg three times daily. At the end of the treatment period, the sleep studies were repeated. There was no significant difference in the incidence, mean duration, or rate per minute of apneic episodes occurring before and with progesterone treatment. Severe hypoxemia during sleep persisted with treatment, as did the occurrence of cardiac arrhythmias. There was a significant improvement in the waking Pao2 with progesterone treatment.