Field studies of acute mountain sickness (AMS) usually include variations in exercise, diet and environmental conditions over days and development of clinically apparent edemas. The purpose of this study was to clarify fluid status in persons developing acute mountain sickness vs. those remaining symptomless during simulated altitude with controlled fluid intake, diet, temperature and without exercise. Ninety-nine exposures of 51 men and women to reduced P_B (426 mm Hg = 16,000 ft = 4,880 m) were carried out for 8-12 hr. AMS was evaluated by Lake Louise (LL) and AMS-C scores near the end of exposure. Serial measurements included fluid balance, electrolyte excretions and plasma concentrations, regulating hormones and free water clearance. Comparison between 16 subjects with lowest AMS scores near the end of exposure ("non-AMS": mean LL=1.0, range=0-2.5) and 16 others with highest AMS scores ("AMS": mean LL=7.4, range=5-11), demonstrated significant fluid retention in AMS beginning within the first 3 hr, resulting from reduced urine flow. Plasma Na⁺ decreased significantly after 6 hr, indicating dilution throughout the total body water. Excretion of Na⁺ and K⁺ trended downward with time in both groups, being lower in AMS after 6 hr, and the urine Na⁺/K⁺ ratio was significantly higher for AMS after 6 hr. Renal compensation for the respiratory alkalosis, plasma renin activity, aldosterone and atrial natriuretic peptide were not different between groups, with the latter tending to rise and aldosterone falling with time of exposure. Anti-diuretic hormone fell in non-AMS and rose in AMS within 90 min of exposure and continued to rise in AMS, closely associated with severity of symptoms and fluid retention.