To investigate the possibility that environmental temperature may exert physiologically significant direct, local effects on subcutaneous adipose tissue temperatures, and its secretion of leptin, we exposed healthy males ( n=12) to repeated cold-water immersion (study 1), and also incubated surgically removed human subcutaneous adipose tissue samples ( n=7) at 27 degrees, 32 degrees and 37 degrees C (study 2). In vivo immersions were conducted over 15 days (60-90 min at 18 degrees C). Regional body temperatures and plasma leptin concentrations were measured before and during immersion. Acute cold exposure suppressed plasma leptin concentration (25 min: -14%, 60 min: -22%, P=0.0001), whilst repeated cold-water immersion was associated with an increase of plasma leptin concentration relative to test day 1 (+19% day 8, +13% day 15, overall P=0.03). Leptin secretion in vitro decreased 3.7-fold as the incubation temperature decreased from 37 degrees to 27 degrees C ( P=0.001). In a compartmental model of leptin turnover in vivo, the measured (local) temperature effect on leptin secretion in vitro was more than able to account for the observed cold-induced decrease in leptin concentration in vivo. We therefore conclude that acute and repeated cold-water immersions have separate and opposing effects on circulating leptin concentrations in humans. Under our experimental conditions, the local effects of reduced subcutaneous adipose tissue temperature may be a more important contributor to the acute effects observed in vivo, than the sympathetically mediated suppression of leptin secretion.