The human pineal gland has been shown to be unresponsive to stress-induced sympathetic activation during the day. However, the effects of stress on human melatonin production have received little investigation at night, when the pinealocytes should be physiologically responsive to noradrenergic stimulation. For this purpose, plasma melatonin and cortisol levels were measured in 7 healthy men (aged 25-34 years), both in resting condition and before and after a physical exercise performed between 23.40 and 24.00 h, 30 min after exposure to bright light (2,500 lx). The exercise consisted in bicycling on a bicycle ergometer at 50% of the personal maximum work capacity (MWC) for 10 min, followed by another 10 min of bicycling at 80% of the MWC. The results clearly showed that physical exercise does not affect light-depressed plasma melatonin levels, whereas it clearly increased plasma cortisol concentrations (p less than 0.002, two-way ANOVA with repeated measures), systolic blood pressure, pulse pressure and heart rate. These findings suggest that the human pineal gland is not responsive to systemic sympathetic activation induced by physical stress even in the middle of the dark phase.