Thanks for providing the reference to the article in the NEJM. I read it several times along with a number of the related articles in the sidebar. Two, including the original article, dismissed endurance training as a protective factor; the others focused on various, more specific factors such as hypoxic ventilatory response, hypoxic cardiac response, arterial O2 saturation, etc. All of them used a target altitude for testing of at least ~4500 meters. A bit of background on my original response is in order. It was based on my personal experience and direct observation of hiking, backpacking, and climbing partners over the last 30 or so years. A number of us have a strong running background, most of us pay a lot of attention to cardio-vascular training, whether it be running or other activities, and most of us suffer very infrequently, if at all, from AMS. Most of our experience, however, is at altitudes in the range of 7000-10000 feet with the occasional foray up to 14000 feet(think Mt Rainier), starting from sea level(Seattle area) and very rapidly, i.e. within 24-30 hours ascending to the target altitude. Such is the nature of weekend climbs in the Pacific Northwest. Dayhikes achieve similar altitudes in a much shorter time. One thing that has stood out is that those most likely to manifest symptoms of AMS do so at the higher end of the abovementioned altitude continuum and are the least cardio-vascularly fit individuals of the bunch. I do not think we are particularly gifted individuals, nor are we all genetic freaks. I do think there is something going on here that has to do with training. A bit of additional data, again anecdotal, to add to the discussion. I had an opportunity to talk with a doctor who went along on an Everest expedition back in the late 80's. He was interested in endurance training as a predictor of success at extreme altitude and found, to his surprise, that it was not those with a marathoning background who were likely to perform well at altitude but, rather, those who excelled at shorter distances, i.e. 5K and 10K. This made a lot of sense to me based on my own experience, both as a runner and in the mountains; marathoners operate almost exclusively well within their aerobic capacity(I am not referring to world class runners here), whereas 5-10K runners are performing at a much higher percentage of VO2 max, often slipping over the anaerobic threshhold in the latter stages of a race. Success is related in both cases to well developed ventilatory capacity and cardiac output to extract the maximum amount of O2 from the atmosphere and deliver it to the working muscles via a dense network of capillaries, but the 5-10K runners encounter conditions closer in one respect to what one experiences at altitude, i.e. O2 shortage. According to the literature on AMS that I have read, low arterial O2 saturation is a major factor associated with AMS, and it seems to make sense to me that an athlete who has trained his/her cardio-vascular system to efficiently extract and deliver O2 in a borderline anaerobic situation has a better chance, not a guarantee by any means, of avoiding AMS. Let me be clear, by the way, that I am not talking about HAPE/HACE-different problem. Nor do I discount the primacy of acclimatization in avoiding AMS. At altitude above 15000 feet, and I have some personal experience there as well, there is no doubt in my mind that proper acclimatization is mandatory if one is to avoid AMS and other more serious problems. What I am saying is that developing a strong cardio-vascular level of fitness can increase your chances of avoiding AMS, especially at the altitudes most of us frequent, with the added benefit of increasing your performance following acclimatization. Along the same lines, a high carb diet, mentioned by a previous poster, makes a whole bunch of sense because glucose (or glucose polymers) carry half the O2 required to oxidize it as part of its molecular structure(C6H12O6 + 6O2 ==> 6CO2 + 6 H2O). Fat and protein have relatively less O2 in their molecular structures and therefore require more O2 from the blood, which is a disadvantage at higher levels of exertion and at higher elevations, especially if one is not fully acclimatized. I have found a high carb diet (in my case Hammer Perpetuem) to be very effective at elevation during the day when I am on the move. With that, I shall retire to the sidelines and enjoy the thread. I hope this isn't the end of it, as it is a subject of considerable importance to anyone who enjoys the high country.