This study investigated the leptin response to vigorous exercise. We examined 12 sedentary subjects (7 males and 5 females) aged 45-59 yr (53 +/- 6.3) with body mass index of 26.1 +/- 8 Kg/m2. The selection of the population was based on the absence of endocrine or any other pathological anomaly. Basal concentrations of leptin, cortisol, insulin and glucose were measured at 08:00 h after an overnight fast. After that the individuals were placed on a computer-controlled ergometer performing a 20-min run at 70% VO2 max under controlled environmental conditions. Blood samples were obtained immediately after the completion of the test. For the following hour, all subjects were placed in the supine position and blood samples were taken at the end of the time period. Statistical evaluation was performed using analysis of variance (ANOVA) for independent variables. Plasma leptin levels exhibited a statistically significant decrease at the end of the 20 min running period (1.5 +/- 0.1 ng/ml vs 3.2 +/- 0.4 ng/ml, p<0.005). Interestingly, after 1 h in the supine position, leptin levels reached the basal values (3.17 +/- 0.1 ng/ml). The concentration of insulin, glucose and cortisol were unaltered during the exercise test (9.8 +/- 1.3 vs 8.85 +/- 1.27 microIU/ml, 95.58 +/- 6.71 mg/dl vs 98.4 +/- 0.78 mg/dl and 10.35 +/- 0.74 microg/dl vs 9.5 +/- 0.7 microg/dl respectively). In conclusion, our data demonstrate a relationship between stressful physical activity and plasma leptin levels in middle-aged subjects.