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Objective: During August of each year, thousands of Nepalese religious pilgrims ascend from 2050 m to 4500 m in 1 to 3 days. Our objectives were to evaluate the incidence of acute mountain sickness (AMS) among this large group of native people, to explore changes in serum electrolytes as subjects ascend to high altitude, and to attempt to determine whether decreased effective circulating volume is associated with the development of AMS., Methods: This was a prospective study with 2 parts. In the first part, demographic, physiologic, and laboratory data were collected from a cohort of 34 pilgrims at both moderate (2050 m) and high altitude (4500 m). Changes that occurred with ascent were compared in subjects who did and did not develop AMS. The second part was a cross sectional study of a different group of 57 pilgrims at the high-altitude site to further determine variables associated with AMS., Results: In the cohort of 34 subjects, Lake Louise score, heart rate, respiratory rate, blood urea nitrogen (BUN), BUN:creatinine ratio, and pH increased at high altitude, whereas oxygen saturation, bicarbonate, creatinine, and PCO2 decreased. Sixteen of these 34 subjects (42%) were diagnosed with AMS; these patients had a statistically significantly lower hematocrit, oxygen saturation, and self-reported water consumption than those without AMS. Of the 57 subjects enrolled in the cross sectional study, 31 (54%) were diagnosed with AMS. These pilgrims had higher heart rates and BUNs than did their non-AMS counterparts., Conclusions: Fifty-two percent of the subjects developed AMS. With ascent to altitude, subjects showed some evidence of decreased effective circulating volume, though there were no clinically significant changes. The data did not show whether decreased circulating volume is a significant risk factor in the development of AMS at high altitude.