To study the effect of medroxyprogesterone on blood gases and cerebral regional oxygenation at high altitude, alone and in conjunction with acetazolamide, and to assess the effect on acute mountain sickness (AMS).Two placebo-controlled trials during rapid ascent to high altitude.In the first trial, 20 participants, and in the second trial, 24 participants.During rapid ascent to 4680m and on rapid ascent to 5200m.In the first trial, participants were randomized to receive medroxyprogesterone 30mg or a placebo twice a day. In the second trial, participants were randomly assigned to one of 4 groups: a placebo twice daily, medroxyprogesterone 30mg twice daily, acetazolamide 250mg plus a placebo twice daily, or acetazolamide 250mg plus medroxyprogesterone 30mg twice daily.Blood gas changes and symptom scores of AMS in both trials and cerebral regional oxygen saturations in the first trial only.Medroxyprogesterone improved peripheral oxygen saturations in both trials and improved Pao 2 in combination with acetazolamide. Cerebral regional oxygen saturation was not altered by medroxyprogesterone. The reduction in symptom scores and in the extent of AMS was not significant in this limited study.Medroxyprogesterone acts as a respiratory stimulant, but the clinical benefit regarding the development of AMS was unproven at high altitude. Combined medroxyprogesterone and acetazolamide gave the best Pao 2.