Circulating leptin concentrations are shown to be influenced not only by hormones, but also by body weight and energy balance. High altitude (HA) exposure induces a daily negative energy balance and stress hormone activation. The aim of our study was to evaluate leptin concentration during both acute and prolonged HA exposure and its correlations with some metabolic and hormonal parameters. Twelve males were studied during a stay at HA (15-20 days at 5,050 m). Blood samples for serum leptin, plasma insulin and 24-h urinary epinephrine (E) and norepinephrine (NE) were collected at sea level (SL), at the arrival at HA (A) and after 12-16 days (C) of stay. Symptoms of Acute Mountain Sickness (AMS) were evaluated using the Lake Louise score and the results showed there was no relationship with leptin concentrations. During the stay, both body mass index and leptin levels significantly decreased in both groups [leptin from 1.88 (1.12) to 1.21 (1.04) ng/ml, P<0.008, in A; and to 1.06 (0.74) ng/ml, P<0.003, in C]. Acute HA exposure induced a clear-cut significant increase of NE ( P<0.001 in A, P<0.003 in C) while E and insulin levels were unchanged in both phases. Moreover, a significant correlation between leptin and NE absolute values, and leptin and insulin variations was found ( r 0.359, P<0.034 and r=0.560, P<0.007, respectively). Exposure to HA induces a decrease in fasting serum leptin concentrations in men. These changes are not linked to symptoms of AMS but to hormonal and energy balance variations, suggesting that leptin is involved in the endocrine and metabolic adaptations occurring during HA exposure.