In this article, an experiential learning activity is described in which 19 university undergraduates made experimental observations on each other to explore physiological adaptations to high altitude. Following 2 wk of didactic sessions and baseline data collection at sea level, the group ascended to a research station at 12,500-ft elevation. Here, teams of three to four students measured the maximal rate of oxygen uptake, cognitive function, hand and foot volume changes, reticulocyte count and hematocrit, urinary pH and 24-h urine volume, athletic performance, and nocturnal blood oxygen saturation. Their data allowed the students to quantify the effect of altitude on the oxygen cascade and to demonstrate the following altitude-related changes: 1) impaired performance on selected cognitive function tests, 2) mild peripheral edema, 3) rapid reticulocytosis, 4) urinary alkalinization and diuresis, 5) impaired aerobic but not anaerobic exercise performance, 6) inverse relationship between blood oxygen saturation and resting heart rate, and 7) regular periodic nocturnal oxygen desaturation events accompanied by heart rate accelerations. The students learned and applied basic statistical techniques to analyze their data, and each team summarized its results in the format of a scientific paper. The students were uniformly enthusiastic about the use of self-directed experimentation to explore the physiology of altitude adaptation and felt that they learned more from this course format than a control group of students felt that they learned from a physiology course taught by the same instructor in the standard classroom/laboratory format.