We previously described a syndrome of congestive heart failure occurring in healthy young men at extreme altitude (Anand et al. Lancet 335: 561-565, 1990). The pathogenesis of this condition is unclear. We therefore measured body fluid compartments, renal blood flow, and a variety of plasma hormones in 10 asymptomatic young men staying above 6,000 m for > 10 wk and compared the results with controls at sea level. Body compartments were measured with isotope dilution techniques and renal blood flow with o-[125I]iodohippurate sodium. There was a marked expansion of all the fluid spaces: total body sodium was 14% above normal (P < 0.05), total body water was 18% above normal (P < 0.05), plasma volume was 33% above normal (P < 0.05), and blood volume was 84.5% above normal (P < 0.001). The effective renal plasma flow was lower than normal by 55% (P < 0.001), but the reduction in the effective renal blood flow was 37% below normal (P < 0.001) because the hematocrit was high (41.6% above normal). Plasma norepinephrine was nearly 3 times normal (P < 0.01), cortisol 3 times normal (P < 0.001), and growth hormone 18 times normal (P < 0.01). Aldosterone was twice normal (P < 0.03). Plasma epinephrine, atrial natriuretic peptide, and plasma renin activity were unchanged. The degree of fluid retention in these normal subjects was similar to that in patients with severe untreated congestive heart failure (Anand et al. Circulation 80: 299-305, 1989), whereas sodium retention and reduction in effective renal blood flow were less.(ABSTRACT TRUNCATED AT 250 WORDS)