To limit the risk of fire and reduce denitrogenation time to prevent decompression sickness to support frequent extravehicular activities on the Moon, a hypobaric (PB = 414 mmHg) and mildly hypoxic (ppO2 = 132 mmHg, 32% O2 - 68% N2) living environment is considered for the Crew Exploration Vehicle (CEV) and Lunar Surface Access Module (LSAM). With acute change in ppO2 from 145-178 mmHg at standard vehicular operating pressure to less than 125 mmHg at desired lunar surface vehicular operating pressures, there is the possibility that some crewmembers may develop symptoms of Acute Mountain Sickness (AMS). The signs and symptoms of AMS (headache plus nausea, dizziness, fatigue, or sleeplessness), could impact crew health and performance on lunar surface missions. An exhaustive literature review on the topic of the physiological effects of reduced ppO2 and absolute pressure as may contribute to the development of altitude symptoms or AMS was performed. The results of the nine most rigorous studies were collated, analyzed and contents on AMS and hypoxia symptoms summarized. There is evidence for an absolute pressure effect per se on AMS, so the higher the altitude for a given hypoxic alveolar O2 partial pressure (PAO2), the greater the AMS response. About 25% of adults are likely to experience mild AMS near 2,000 m altitude following a rapid ascent from sea level while breathing air (6,500 feet, acute PAO2 = 75 mmHg). The operational experience with the Shuttle staged denitrogenation protocol at 528 mmHg (3,048 m) while breathing 26.5% O2 (acute PAO2 = 85 mmHg) in astronauts adapting to microgravity suggests a similar likely experience in the proposed CEV environment. We believe the risk of mild AMS is greater given a PAO2 of 77 mmHg at 4,876 m altitude while breathing 32% O2 than at 1,828 m altitude while breathing 21% O2. Only susceptible astronauts would develop mild and transient AMS with prolonged exposure to 414 mmHg (4,876 m) while breathing 32% O2 (acute PAO2 = 77 mmHg). So the following may be employed for operational risk reduction: 1) develop procedures to increase PB as needed in the CEV, and use a gradual or staged reduction in cabin pressure during lunar outbound; 2) train crews for symptoms of hypoxia, to allow early recognition and consider pre-adaptation of crews to a hypoxic environment prior to launch, 3) consider prophylactic acetazolamide for acute pressure changes and be prepared to treat any AMS associated symptoms early with both carbonic anhydrase inhibitors and supplemental oxygen
