We investigated whether cold exposure affects circulating leptin in humans. Five women (age, 32+/-4 years; body mass index, 23.1+/-1.7 kg/m2) participated in two separate trials. Subjects sat at room temperature ([RT] 24.8 degrees+/-0.3 degrees C) or in the cold (6.3 degrees+/-0.5 degrees C) for 90 minutes. During RT exposure, plasma leptin and norepinephrine were unchanged over time. Cold exposure significantly decreased plasma leptin by 14%, 17%, and 22% at 30, 60, and 90 minutes, respectively (temperature x time interaction, P < .04). Plasma norepinephrine increased by 400% to 500% (P < .001) and plasma glycerol increased by 110% over baseline during cold exposure (temperature effect, P < .005). We conclude that circulating leptin decreases during cold exposure, probably as a result of activation of the sympathetic nervous system (SNS).